Tetrazole compounds and pharmaceutical agents containing such derivative as an active ingredient

ABSTRACT

A tetrazole derivatives of formula (I)                    
     wherein 
     R 1  is H, alkyl, alkoxy, carbocyclic ring, hetero ring, alkyl or alkoxy substituted by carbocyclic ring or hetero ring, etc.; AA 1  is bond or                    
      AA 2  is bond or                    
      AA 1  and AA 2 , together, may have the formula (a);                    
      Y is the formula (b)                    
     (in which Tet ring is tetrazole; Z is alkylene, alkenylene, O, S, SO, SO 2 , NR 26 , methylene in alkylene replaced by O, S, —SO—, —SO 2 — or —NR 26 —; E is H, alkyl, COOR 27  or                    
      in which Cyc is carbocyclic ring or hetero ring); 
     a non-toxic salt thereof, an acid addition salt thereof or a hydrate thereof which has a pharmaceutical agents as an active ingredient. The compound of the formula (I) has an inhibitory effect on interleukin-1β converting enzyme, therefore, they are useful for prevention and/or treatment of various kinds of inflammatory disease.

This is a divisional of application Ser. No. 09/101,004 filed Jun. 29,1998, U.S. Pat. No. 6,136,834 the disclosure of which is incorporatedherein by reference, which application is a national stage filing under35 U.S.C. §371 of PCT JP/96/03801, filed Dec. 26, 1996.

FIELD OF THE INVENTION

This invention relates to tetrazole compounds. More particularly, thisinvention relates to:

(1) tetrazole compounds having interleukin-1β converting enzymeinhibitory activity of the following formula (I):

 wherein all of the symbols have the same meanings as describedhereinafter, or a non-toxic salt thereof, an acid addition salt thereofor a hydrate thereof;

(2) processes for the preparation thereof; and

(3) pharmaceutical agents containing such devivative as an activeingredient.

BACKGROUND OF THE INVENTION

Interleukin 1 (IL-1) is a key cytokine that directly or indirectlyparticipates in the regulation of, for example, the immune system,hemopoietic system and neuroendocrine system, and thus, has a crucialphysiological role. There are two types of IL-1, which have differentisoelectric points (IL-1α: pl=5, IL-1β: pl=7). Both of these areproduced as a precursor having molecular weight of 31 Kd. The IL-1βprecursor does not bind to the IL receptor nor exerts a biologicalfunction. The IL-1β converting enzyme (ICE) cleaves the precursorprotein between Asp 116 and Ala 117 and converts into an active IL-1βmature form having a molecular weight of 17 Kd. Following the cleavage,IL-1β is secreted, binds to the receptor and triggers various biologicalactivities (Ref. The New England Journal of Medicine, 328, 106 (1993)).

The inhibition of ICE enzymatic activity leads to prevention ofconversion of the IL-1β precursor into the mature form and hence resultsin blockage of IL-1 biological activity. There are many possible targetdiseases for ICE inhibitors, for example, prevention and/or treatment ofinsulin dependent diabetes (type 1), autoimmune diseases, includingmultiple sclerosis, immune diseases, such as acute or delayed typehypersensitivity, infectious diseases, infection complications, septicshock, acute or chronic inflammatory diseases, such as arthritis,colitis, glomelular nephritis, hepatitis, pancreatitis, reperfusioninjury, cholangeitis, encephalitis, endocarditis, myocarditis andvasculitis, neural diseases, such as Alzheimer's disease and Parkinson'sdisease, bone or cartilage-resorption diseases, Crohn's disease, osteoarthritis etc.

It is believed that ICE and/or ICE-like cystein proteases play importantroles in cell death by apoptosis. Therefore it is possible that an ICEinhibitor may be used in the prevention and/or treatment of diseasesresulting from apoptosis disorders, such as infection, reduction orenhancement of immune or central nervous system function, neoplasm etc.Diseases associated with apoptosis disorders are as follows; AIDS, ARC(AIDS related complex), adult T cell leukemia, hairy cell (pilocytic)leukemia, myelosis, respiratory dysfunction, arthropathy, HIV or HTLV-Irelated diseases, such as uveitis, virus related diseases, such ashepatitis C, neoplasm, diffuse collagen diseases, such as systemic lupuserythematosis or rheumatoid arthritis, autoimmune diseases, such asulcerative colitis, Sjogren's syndrome, primary binary cirrhosis,idiopathic thrombocytopnic purpura, autoimmonohaemolytic anemia, severemyasthenia, insulin dependent (type I) diabetes, osteodysplasiasyndrome, periodic thrombocytopenia, aplastic anemia, idiopathicthrombocytopenia, various diseases which accompany thrombocytopenia,such as disseminated intravascular coagulation, hepatic diseases,including hepatitis (type C, A, B, or F virus borne or drug mediated)and hepatic cirrhosis, Alzheimer's disease, dementia, such as Alzheimertype senile dementia, cerebral vascular disturbance, neuro-degenerativediseases, adult dyspnea syndrome, infection, hyperplasia of theprostate, myoma of the uterus, asthma bronchiole, arteriosclerosis,various kinds of congenital teratoma, nephritis, senile cataract,chronic fatigue syndrome, myodystrophy, peripheral nervous disturbance,and so on (Ref. The New England Journal of Medicine, 328, 106-113(1993), Arthritis & Rheumatism, 39, 1092 (1996)).

RELATED ARTS

Compounds having an inhibitory activity on IL-1β converting enzyme (ICE)are known. The sequence of the ICE cleavage site of pre-IL-1β(Tyr-Val-His-Asp) has high affinity with ICE. Substrate analoginhibitors which are chemically modified and based on the abovesubstrate sequence, for example, a compound of formula (X):

wherein

Y^(X) is

 ,or

R^(1X) is

(a) a substituted C1-12 alkyl (in which a substituent is hydrogen,hydroxy etc.) or

(b) an aryl C1-6 alkyl (in which aryl is phenyl, naphthyl, pyridyl,furyl, thienyl, thiazolyl, isothiazolyl, imidazolyl, benzoimidazolyl,pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, benzofuryl, benzothienyl,pyrazolyl, indolyl, purinyl or isooxazolyl), wherein the aryl can bemono-substituted or di-substituted (in which a substituent is a C1-6alkyl, halogen, hydroxyl, C1-6 alkylcarbonyl etc.);

R^(2X) is

(a) hydrogen,

(in which R^(3X) is

(1) a substituted C1-12 alkyl (in which a substituent is hydrogen,hydroxy etc.), or

(2) an aryl C1-6 alkyl or substituted aryl C1-6 alkyl as hereinbeforedefined (in which an aryl may be mono-substituted or di-substituted byC1-6 alkyl, halogen, hydroxyl, C1-6 alkylcarbonyl etc.);

R^(4X) and R^(5X) are each hydrogen, hydroxyl etc.; and

R^(6X) is

(1) hydrogen,

(2) a substituted C1-6 alkyl (in which a substituent is hydrogen,hydroxyl etc.),

(3) an aryl C1-6 alkyl (in which alkyl is substituted by hydrogen, oxo,C1-3 alkyl etc., aryl has the same meaning as hereinbefore defined, saidaryl is mono-substituted or di-substituted, said substituent is C1-6alkyl, halogen, hydroxyl, C1-6 alkylcarbonyl etc.),

(4) a C1-6 alkylaminocarbonyl C1-6 alkyl or C1-6 alkylcarbonylamino C1-6alkyl,

(5) an arylaminocarbonyl C1-6 alkyl or arylcarbonylamino C1-6 alkyl (inwhich aryl has the same meaning as hereinbefore defined, said aryl ismono-substituted or di-substituted, said substituent is C1-6 alkyl,halogen, hydroxyl, C1-6 alkylcarbonyl etc.) or

(6) an aryl C1-6 alkylaminocarbonyl C1-6 alkyl or aryl C1-6alkylcarbonylamino C1-6 alkyl (in which aryl has the same meaning ashereinbefore defined, said aryl is mono-substituted or di-substituted,said substituent is C1-6 alkyl, halogen, hydroxyl, C1-6 alkylcarbonyletc.) etc.;

AA^(1X) is a bond etc.;

AA^(2X) is a bond or; and

AA^(3X) is a bond or

 (wherein R^(8X) and R^(9X) is

(a) hydrogen,

(b) a substituted C1-6 alkyl (in which a substituent is hydrogen,hydroxyl etc.) or

(c) an aryl C1-6 alkyl (in which aryl has the same meaning ashereinbefore defined, said aryl is mono-substituted or di-substituted,said substituent is C1-6 alkyl, halogen, hydroxyl, C1-6 alkylcarbonyl,etc.)) (with the proviso that, definitions not related are omitted) aredisclosed as having an inhibitory activity on ICE (see EP 519748).

The compounds of formula (Y):

R^(Y)—[A^(1Y)—A^(2Y)]_(nY)—A^(3Y)—A^(4Y)—X^(Y)—A^(5Y)  (Y)

wherein

R^(Y) is hydrogen, an amino protecting group or benzyloxy, which may beoptionally substituted by a ring;

nY is 0 or 1;

A^(1Y) is Val, Leu, Ala, Ile or trimethylsilyl-Ala;

A^(2Y) is Phe or Tyr;

A^(3Y) is Val, Leu, Ala, Ile, trimethylsilyl-Ala or a divalent radicalgroup:

(in which ring A^(Y) may be optionally substituted by hydroxy or C1-4alkoxy); A^(4Y) is a bond or

(in which R^(1Y) is hydrogen or C1-4 alkyl, and

Y^(1Y) is a residue bonded to the α-carbon atom of an optionallyprotected α-amino acid);

wherein

A^(3Y) and A^(4Y) together may form:

(wherein Y^(1Y) has the same meaning as hereinbefore defined, and R^(1Y)and R^(1aY) are combined to form —(CH₂)_(mY)—(in which mY is 2, 3, 4 or5));

X^(Y) is a divalent radical group:

(wherein R^(6Y) is hydrogen or C1-4 alkyl); and

A^(5Y) is hydrogen, CF₃, —Z^(1Y)—Z^(2Y)—Y^(2Y) (in which Z^(1Y) andZ^(2Y) is each, independently, a bond or an α-amino acid residue andY^(2Y) is NH₂, C1-4 alkylamino, di-(C1-4 alkyl)amino or hetero ringbonded to the Z^(2Y) nitrogen), —CH₂—X^(1Y)—Y^(3Y) (in which X^(1Y) is Oor S and Y^(3Y) is heteroaryl) or —CH₂—Y^(3Y) wherein Y^(3Y) is aspreviously defined)

(with the proviso that, definitions not related are omitted) have aninhibitory activity on IL-1β release (see WO 93/09135).

Further, it is disclosed that compounds of formula (Z):

R^(Z)—A^(1Z)—A^(2Z)—X^(Z)—A^(3Z)  (Z)

wherein

R^(Z) is hydrogen, an amino or hydroxy protecting group or benzyloxywhich may be optionally substituted by a ring;

A^(1Z) is an α-hydroxy acid, amino acid residue or thiocarbonylanalogue, each with an optionally protected side chain, or

(in which ring A^(Z) may be optionally substituted by hydroxy or C1-4alkoxy and R^(aZ) is CO or CS);

A^(2Z) is an α-hydroxy acid, —NH—CHR^(3Z)—CO— (in which R^(3Z) is anoptionally protected side chain of an α-amino acid);

X^(Z) is

 ,or

(in which R^(7Z) is —CO₂H, —CONHOH or a bioisosteric group); and

A^(3Z) is —CH₂—X^(1Z)—CO—Y^(1Z), —CH₂—O—Y^(2Z) or —CH₂—S—Y^(3Z) (inwhich X^(1Z) is O or S, Y^(1Z) is an aliphatic ring, optionallysubstituted with aryl, diphenylmethyl, optionally substituted by a ring,piperidino or optionally substituted mono, di or tricyclic heteroaryl,Y^(2Z) is an aliphatic ring, diphenylmethyl, optionally substituted by aring, or optionally substituted di or tricyclic heteroaryl etc. andY^(3Z) is an aliphatic ring, tri-(C1-4 alkyl)methylcarbonyl, di-(C1-4alkyl) aminothiocarbonyl, 4-nitrophenyl, 2,6-dichloro-benzoyl,2,3,6-trichloro-4-pyridyl, 5-membered heterocyclic ring containing anitrogen atom or optionally substituted di or tricyclic heteroaryl,etc.) etc.; and

A^(1Z) and A^(2Z) may form

(in which R^(1aZ) and R^(5Z) together make form C2-5 alkylene or C2-5alkenylene and Y^(5Z) is an optionally protected side chain of anα-amino acid, etc.)

(with the proviso that, definitions not related are omitted) have aninhibitory activity on IL-1β release (see EP 618223).

Furthermore, it is disclosed that compounds of formula (W):

wherein

nW is 0-4;

Y^(W) is

 wherein when R^(3W) is O, Y^(W) is

(in which R^(2W) is hydrogen or deuterium;

R^(3W) is O, OH, OR^(6W), NR^(6W) OR^(7W) or NR^(6W)R^(7W);

R^(6W) and R^(7W) each, independently, is hydrogen, alkyl, aralkyl,heteroaralkyl, aryl or heteroaryl;

R^(4W) is hydrogen or alkyl;

R^(5W) is hydrogen, alkyl, alkenyl, aryl, heteroaryl, aralkyl,heteroaralkyl, halogen, haloalkyl, nitro or cyano, HET^(W) isheteroaryl);

AA^(W) is

(in which R^(6W) and R^(7W) have the same meaning as hereinbeforedefined and

R^(11W) is (CR^(6W)R^(7W))₀₋₆—R^(12W) (wherein R^(12W) is aryl,heteroaryl or optionally selected from hereinbefore described R^(5W)))or an amino acid; and

R^(1W) is R¹²W—CO— or R^(12W)SO₂— (wherein R^(12W) has the same meaningas hereinbefore defined)

(with the proviso that, definitions not related are omitted) have aninhibitory activity on IL-1β converting enzyme (see CA 2125021)

PURPOSE OF THE INVENTION

Energetic investigations have been carried out to discover new compoundshaving inhibitory activity on IL-1β converting enzyme. As a result, thepresent inventors have achieved that goal by a tetrazole compound offormula (I).

COMPARISON OF THE INVENTION AND RELATED ARTS

The tetrazole compounds of the present invention are newly synthesizedand therefore, are quite novel.

To summarize, in the compound of formula (X) known in the art (EP519748), R^(6X) of Y^(X) can represent aryl C1-6 alkyl. But, the arylgroup does not include a tetrazole. On the other hand, in the compoundof the present invention, Y essentially is the tetrazole group.Therefore, it can be said that the compounds of the present inventionhave a chemical structure quite different from the compounds of formula(X). A representative example of formula (X) is compound (X-1).

In the compound of formula (Y) of WO93/09135, Y^(3Y) of A^(5Y) can be aheteroaryl group. Further, exemplification of the heteroaryl groupincludes a tetrazole group. But, no substituents of the heteroaryl groupare disclosed in detail in WO93/09135. On the other hand, a compound ofthe present invention has a ring essentially as substituents of thetetrazole of Y. It can be said that the compounds of the presentinvention have a chemical structure quite different from the compoundsof formula (Y). Representative examples of formula (Y) are compounds(Y-1) and (Y-2).

Further, in a compound of formula (Z), EP 618223, Y^(3Z) of A^(3Z) canrepresent a heteroaryl group. Further, exemplification of the heteroarylgroup includes a tetrazole. But, only C1-4 alkyl is disclosed assubstituents of the heteroaryl group. On the other hand, a compound ofthe present invention has a ring as a substituent of the tetrazole of Y.Therefore, it can be said that the compounds of the present inventionhave a chemical structure quite different from the compounds of formula(Z). Furthermore, in the compounds of formula (Z), Y^(3Z) as aheteroaryl group is essentially bonded to a hetero atom (oxygen orsulfur atom). On the other hand, in the present invention, the tetrazolegroup of Y is bonded to a carbon atom. Thus, for another reason,compounds of formula (I) of the present invention have a chemicalstructure quite different from a compound of formula (Z). Arepresentative example of a compound of formula (Z) is compound (Z-1).

Furthermore, in the compounds of formula (W) of CA 21 25021, HET^(W) ofY^(W) can be a heteroaryl group. Further, exemplification of theheteroaryl group includes a tetrazole group. But, there are nopreparative examples of compounds in which a heteroaryl group is atetrazole. Additionally, in the compound of formula (W), HET^(W) as aheteroaryl is bonded to a hetero atom (oxygen atom). On the other hand,in the present invention, the tetrazole group Y is bonded to a carbonatom. Thus, compounds of formula (I) of the present invention have achemical structure quite different from compound of formula (W). Arepresentative compound of formula (W) is compound (W-1).

Therefore, the compounds of the present invention have a chemicalstructure quite different from the compounds of formulae (X), (Y), (Z)and (W) known in the art. The instant compounds are novel and notpreviously described.

Therefore, the present inventors-have found that tetrazole compounds offormula (I) have an inhibitory activity on IL-1β converting enzyme evenif a hetero atom dose not exist between a ketone group and a ring. Thatobservation is quite unexpected from what is known in the art, and hasbeen confirmed from experiments by the present inventors for the firsttime.

SUMMARY OF THE INVENTION

The present invention is related to:

1) A tetrazole derivatives of the formula (I)

 wherein R is a hydrogen atom,

(in which J is bond, C1-6 alkylene, C1-6 oxyalkylene, C1-6aminoalkylene, C1-6 thioalkylene, C2-6 alkenylene, carbocyclic ring orhetero ring, carbocyclic ring and hetero ring may be substituted by C1-4alkyl, with the proviso that, when J contains oxygen, nitrogen or sulfuratom, it is bond to C═O or S(O)_(m) group in R),

R¹ is

1) C1-8 alkyl,

2) C1-8 alkoxy,

3) C2-8 alkenyl,

4) C2-8 alkenyloxy,

5) C1-8 alkylamino,

6) di(C1-8 alkyl)amino,

7) C1-8 alkylthio,

8) Cyc¹ (in which Cyc¹ is a carbocyclic ring or hetero ring, and Cyc¹may be substituted by 1 to 5 substituents selected from a hydrogen atom,C1-8 alkyl, phenyl, phenyloxy, C1-8 alkyl substituted by phenyl, ahalogen atom, nitro, trifluoromethyl, nitrile, keto, —OR², —NR²R³,—S(O)R², —SO₂R², —COOR or —COR², wherein R² is a hydrogen atom, C1-8alkyl, phenyl or C1-4 alkyl substituted by phenyl, R³ is a hydrogenatom, C1-8 alkyl, phenyl or C1-4 alkyl substituted by phenyl, C2-5 acyl,or R2 and R3, taken together bonded to nitrogen atom, represent heteroring),

9) Cyc¹—O—,

10) Cyc¹—S—,

11) Cyc¹—CO—,

12) C1-8 alkyl, C1-8 alkoxy, C1-8 alkylamino, di(C1-8 alkyl)amino orC1-8 alkylthio mono or di-substituted by Cyc¹, Cyc¹—O—, Cyc¹—S—, orCyc¹—CO—,

13) trifluoromethyl,

14) Cyc¹—CO—NH—CH₂—,

15) amino,

16) benzyloxycarbonyl,

17) C2-5 acylamino, or

18) C1-8 alkoxy substituted by C1-8 alkoxy,

m is 0 or 1-2,

with the proviso that,

(1) when m is 0, then —S(O)_(m)— is not directly bonded to nitrogen orsulfur atom, and

(2) when m is 1, then —S(O)_(m)— is not directly bonded to sulfur atom,

AA¹ is

1) a bond or

2)

(in which R⁴ is

(1) a hydrogen atom,

(2) C1-8 alkyl,

(3) Cyc² (in which Cyc² is a carbocyclic ring or hetero ring, and Cyc²may be substituted by 1 to 5 substituents selected from a hydrogen atom,C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl, a halogen atom,nitro, trifluoromethyl, nitrile, tetrazole, —OR⁵, —NR⁵R⁶, —SR⁵, —COOR⁵or —COR⁵ wherein R⁵ and R⁶ each, independently, is a hydrogen atom, C1-4alkyl, phenyl or C1-4 alkyl substituted by phenyl) or

(4) C1-8 alkyl substituted by a substituent selected from —OR⁷, —NR⁷R⁸,—SR⁷, COOR⁷, —COR⁷, —CONH₂, —NR⁷—CO—NR⁷R⁸, guanidino or Cyc² (in whichR⁷ and R⁸ each, independently, is a hydrogen atom, C1-4 alkyl, phenyl orC1-4 alkyl substituted by phenyl),

AA² is

1) a bond or

2)

(in which R⁹ and R¹⁰ each, independently, is

(1) a hydrogen atom,

(2) C1-8 alkyl,

(3) Cyc³ (in which Cyc³ is a carbocyclic ring or hetero ring, and Cyc³may be substituted by 1 to 5 substituents selected from a hydrogen atom,C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl, a halogen atom,nitro, trifluoromethyl, nitrile, tetrazole, —OR¹¹, —NR¹¹R¹², —SR¹¹,—COOR¹¹ or —COR¹¹, wherein R¹¹ and R¹² each, independently, is ahydrogen atom, C1-4 alkyl, phenyl or C1-4 alkyl substituted by phenyl),

(4) C1-8 alkyl substituted by a substituent selected from —OR¹³,—NR¹³R¹⁴, —SR¹³, —COOR¹³, —COR¹³, —CONH₂, —NR¹³—CO—NR¹³R¹⁴, guanidino orCyc³ (in which R¹³ is a hydrogen atom, C1-4 alkyl, phenyl or C1-4 alkylsubstituted by phenyl, R¹⁴ is a hydrogen atom, C1-4 alkyl, phenyl, C1-4alkyl substituted by phenyl, t-butyloxycarbonyl or benzyloxycarbonyl) or

(5) R⁹ and R¹⁰, together, is a C1-6 alkylene or C2-6 alkenylene),

AA¹ and AA², together, may have the formula

in which R¹⁵ and R¹⁶ each, independently, is a hydrogen atom, C1-4alkyl, phenyl or C1-4 alkyl substituted by phenyl (with the provisothat, C1-4 alkyl or phenyl may be substituted by C1-4 alkyl, C1-4alkoxy, a halogen atom, trifluoromethyl or phenyl),

R¹⁷ is

(1) a hydrogen atom,

(2) C1-8 alkyl,

(3) Cyc³ (in which Cyc³ has the same meaning as hereinbefore defined) or

(4) C1-8 alkyl substituted by a substituent selected from —OR¹³,—NR¹³R¹⁴, —SR¹³, —COOR¹³, —COR¹³, —CONH₂, —NR¹³—CO—NR¹³R¹⁴, guanidino orCyc³ (in which R¹³ and R¹⁴ have the same meaning as hereinbeforedefined),

q is 2-12,

with the proviso that, a carbon atom in —(CH₂)_(q)— may be replaced byan oxygen atom, sulfur atom, —SO—, —SO₂— or —NR¹⁸— (in which R¹⁸ is ahydrogen atom, C1-4 alkyl, phenyl or C1-4 alkyl substituted by phenyl),or

two hydrogen atom at ortho positions are replaced by a double bond and

Y is

in which R¹⁹ is a hydrogen atom, C1-8 alkyl, phenyl or C1-4 alkylsubstituted by phenyl,

n is 1-4,

 is

 or

Z is

1) C1-6 alkylene,

2) C2-6 alkenylene,

3) oxygen atom,

4) sulfur atom,

5) —CO—,

6) —SO—,

7) —SO₂—,

8) —NR²⁶— (in which R²⁶ is a hydrogen atom, C1-4 alkyl, phenyl, C1-4alkyl substituted by phenyl), or

9) a carbon atom in C1-6 alkylene replaced by an oxygen atom, sulfuratom, —CO—, —SO—, —SO₂— or —NR²⁶— (in which R²⁶ is the same meaning ashereinbefore defined),

with the proviso that, Z is bonded directly to the carbon atom on atetrazole ring,

E is a hydrogen atom, a halogen atom, C1-4 alkyl, —COOR²⁷ (in which R²⁷is a hydrogen atom, C1-4 alkyl, phenyl, C1-4 substituted by phenyl),—CONR²⁸R²⁹ (in which R²⁸H and R²⁹ each, independently, is a hydrogenatom, C1-4 alkyl, phenyl, C1-4 substituted by phenyl or R²⁸ and R²⁹,taken together, boned to nitrogen atom represent hetero ring), —NR²⁸R²⁹(in which R²⁸ and R²⁹ are the same meaning as hereinbefore defined), or

 (in which

 is carbocyclic ring or hetero ring,

R²⁰ is

1) a hydrogen atom,

2) C1-8 alkyl,

3) a halogen atom,

4) nitro,

5) trifluoromethyl,

6) nitrile,

7) —OR²²,

8) —NR²²R²³,

9) —SR²²,

10) —COOR²²,

11) —COR²²,

12) —CONR²⁸R²⁹ (in which R²⁸ and R²⁹ are the same meaning ashereinbefore defined),

13) Cyc⁴ (in which Cyc⁴ is a carbocyclic ring or hetero ring, and Cyc⁴may be substituted by 1 to 5 substituents selected from a hydrogen atom,C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl, a halogen atom,nitro, trifluoromethyl, nitrile, tetrazole, —OR²⁴, —NR²⁴R²⁵, —SR²⁴,—COOR²⁴ or —COR²⁴ (in which R²⁴ and R²⁵ each, independently, is ahydrogen atom, C1-4 alkyl, phenyl or C1-4 alkyl substituted by phenyl)),or

14) C1-8 alkyl substituted by Cyc⁴ (in which Cyc⁴ is the same meaning ashereinbefore defined),

R²² is a hydrogen atom, C1-4 alkyl, phenyl or C1-4 alkyl substituted byphenyl,

R²³ is a hydrogen atom, C1-4 alkyl, phenyl, C1-4 alkyl substituted byphenyl, C2-5 acyl or trifluoromethylcarbonyl,

p is 1-5), or

—Z—E is a halogen atom, trifluoromethyl, C1-4 alkyl di-substituted byphenyl or tri(C1-4 alkyl)silyl,

with the proviso that,

(1) when Z is C1-6 alkylene or C2-6 alkenylene, then E is not a hydrogenatom or C1-4 alkyl, or

(2) when Z is —SO—, then E is not a hydrogen atom, or a non-toxic saltthereof, an acid addition salt thereof or a hydrate thereof,

2) processes for the preparation thereof and

3) pharmaceutical agents containing such a derivative as an activeingredient.

Throughout the specification, including claims, it may be easilyunderstood by those skilled in the art, that all isomers are included inthe present invention. For example, the alkyl, alkoxy and alkylenegroups include straight-chain and also branched-chain ones. Accordingly,all isomers produced by the existence of asymmetric carbon atoms areincluded in the present invention when branched-chain alkyl, alkoxy,alkylene, etc. exist.

In formula (I), C1-8 alkyl represented by substituent of Cyc¹,substituent of Cyc², substituent of Cyc³, R¹, R², R³, R⁴, R⁹, R¹⁰, R¹⁷,R¹⁹ and R²⁰, C1-8 alkyl mono or di-substituted by Cyc¹, Cyc¹—O—, Cyc¹—S—or Cyc¹—CO—, C1-8 alkyl substituted by Cyc⁴, C1-8 alkyl substituted by agroup selected from —OR⁷, —NR⁷R⁸, —SR⁷, —COOR⁷, —COR⁷, —CONH₂,—NR⁷—CO—NR⁸, guanidino and Cyc² and C1-8 alkyl substituted by a groupselected from —OR¹³, —NR¹³R¹⁴, —SR¹³, —COOR¹³, —COR¹³, —CONH₂,—NR¹³—CO—NR¹⁴, guanidino and Cyc³ each means methyl, ethyl, propyl,butyl, pentyl, hexyl, heptyl, octyl and an isomer thereof.

In formula (I), C1-8 alkylamino represented by R¹ and C1-8 alkylaminomono or di-substituted by Cyc¹, Cyc¹—O—, Cyc¹—S— or Cyc¹—CO— each meansmethyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl and an isomerthereof, which are substituted by an amino group.

In formula (I), di(C1-8 alkyl)amino represented by R¹ and di(C1-8alkyl)amino mono or di-substituted by Cyc¹, Cyc¹—O—, Cyc¹—S— or Cyc¹—CO—each means methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyland an isomer thereof, which are each independently di-substituted by anamino group on nitrogen atom.

In formula (I), C1-8 alkylthio represented by R¹ and C1-8 alkylthio monoor di-substituted by Cyc¹, Cyc¹—O—, Cyc¹—S— or Cyc¹—CO— each meansthiomethyl, thioethyl, thiopropyl, thiobutyl, thiopentyl, thiohexyl,thioheptyl, thiooctyl and an isomer thereof.

In formula (I), C1-8 alkoxy represented by R¹ and C1-8 alkoxy mono ordi-substituted by Cyc¹, Cyc¹—O—, Cyc¹—S— or Cyc¹—CO— each means methoxy,ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy and anisomer thereof.

In formula (I), C1-8 alkoxy substituted by C1-8 alkoxy represented by R¹means methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy,octyloxy and the isomer thereof, which are substituted by a methoxy,ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy andthe isomer thereof.

In formula (I), C1-4 alkyl represented by a substituent of carbocyclicring , substituent of hetero ring, substituent of R¹⁵, substituent ofR¹⁶, R⁵, R⁶, R⁷, R⁸, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁸, R²², R²³, R²⁴,R²⁵, R²⁶, R²⁷, R²⁸, R²⁹ and E means methyl, ethyl, propyl, butyl and anisomer thereof.

In formula (I), C1-4 alkoxy represented by R¹⁵ and R¹⁶ mean methoxy,ethoxy, propoxy, butoxy and an isomer thereof.

In formula (I), C1-4 alkyl substituted by phenyl represented bysubstituent of Cyc², substituent of Cyc³, substituent of Cyc⁴, R², R³,R⁵, R⁶, R⁷, R⁸, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁸, R¹⁹, R²², R^(23, R)²⁴, R²⁵, R²⁶, R²⁷, R²⁸ and R²⁹ means methyl, ethyl, propyl, butyl andthe isomer thereof, which are substituted by a phenyl group.

In formula (I), C1-8 alkyl substituted by phenyl represented bysubstituent of Cyc¹ means methyl, ethyl, propyl, butyl, pentyl, hexyl,heptyl, octyl and the isomer thereof, which are substituted by a phenylgroup.

In formula (I), a halogen atom represented by a substituent of R¹⁵ andR¹⁶, substituent of Cyc¹, substituent of Cyc², substituent of Cyc³,substituent of Cyc⁴, R²⁰, E and —Z—E means fluorine, chlorine, bromineand iodine.

In formula (I), C1-6 alkylene represented by J, Z, and R⁹ and R¹⁰, takentogether, means methylene, ethylene, trimethylene, tetramethylene,pentamethylene, hexamethylene and an isomer thereof.

In formula (I), C1-6 oxyalkylene represented by J means oxymethylene,oxyethylene, oxytrimethylene, oxytetramethylene, oxypentamethylene,oxyhexamethylene and an isomer thereof.

In formula (I), C1-6 aminoalkylene represented by J meansaminomethylene, aminoethylene, aminotrimethylene, aminotetramethylene,aminopentamethylene, aminohexamethylene and an isomer thereof.

In formula (I), C1-6 thioalkylene represented by J means thiomethylene,thioethylene, thiotrimethylene, thiotetramethylene, thiopentamethylene,thiohexamethylene and an isomer thereof.

In formula (I), C2-6 alkenylene represented by J, Z, and R⁹ and R¹⁰,taken together, means vinylene, propenylene, butenylene, pentenylene,hexenylene, butadienylene, pentadienylene, hexadienylene, hexatrienyleneand an isomer thereof.

In formula (I), C2-8 alkenyl represented by R¹ means vinyl, propenyl,butenyl, pentenyl, hexenyl, heptenyl, octenyl, butadienyl, pentadienyl,hexadienyl, heptadienyl, octadienyl, hexatrienyl, heptatrienyl,octatrienyl and an isomer thereof.

In formula (I), C2-8 alkenyloxy represented by R¹ means vinyloxy,propenyloxy, butenyloxy, pentenyloxy, hexenyloxy, heptenyloxy,octenyloxy, butadienyloxy, pentadienyloxy, hexadienyloxy,heptadienyloxy, octadienyloxy, hexatrienyloxy, heptatrienyloxy,octatrienyloxy and an isomer thereof.

In formula (I), C2-5 acyl represented by R³ and R²³ means acetyl,propionyl, butyryl, valeryl and an isomer thereof.

In formula (I), C2-5 acylamino represented by R¹ means acetylamino,propionylamino, butyrylamino, valerylamino and an isomer thereof.

In formula (I), tri(C1-4 alkyl)silyl represented by —Z—E means eachindependent tri-substituted by methyl, ethyl, propyl, butyl and theisomer thereof, on silicon atom.

In formula (I), a carbocyclic ring represented by J Cyc¹, Cyc², Cyc³,Cyc⁴ and

means a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring. Forexample, a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ringinclude cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclopentadiene, benzene, pentalene, indene, naphthalene, azulene ringetc.

In formula (I), a hetero ring represented by J, Cyc¹, Cyc², Cyc³, Cyc⁴and

means a 5-18 membered mono-cyclic, bi-cyclic or tri-cyclic hetero ringcontaining 1-2 nitrogen atoms, one oxygen atom or one sulfur atom. Forexample, a 5-18 membered mono-cyclic, bi-cyclic or tri-cyclic heteroring containing 1-3 nitrogen atoms, one oxygen atom or one sulfur atomincludes pyrrole, imidazole, triazole, pyrazole, pyridine, pyrazine,pyrimidine, pyridazine, azepine, diazepine, furan, pyran, oxepine,oxazepine, thiazoe, thiaine (thiopyran), thiepine, oxazole, isooxazole,thiazole, isothiazole, oxadiazole, oxazine, oxadiazine, oxazepine,oxadiazepine, thiadiazole, thiazine, thiadiazine, thiazepine,thiadiazepine, indole, isoindole, benzofuran, isobenzofuran,benzothiophene, isobenzothiophene, indazole, quinoline, isoquinoline,phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline,benzoxazole, benzothiazole, benzoimidazole, pyrroline, pyrrolidine,imidazoline, imidazolidine, pyrazoline, pyrazolidine, piperidine,piperazine, tetrahydropyrimidine, tetrahydropyridazine, dihydrofuran,tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene,tetrahydrothiazoe, dihydrothiaine (dihydrothiopyran), tetrahydrothiaine(tetrahydrothiopyran), dihydrooxazole, tetrahydrooxazole,dihydroisooxazole, tetrahydroisooxazole, dihydrothiazole,tetrahydrothiazole, dihydroisothiazole, tetrahydroisothiazole,morpholine, thiomorpholine, indoline, isoindoline, dihydrobenzofuran,perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran,dihydrobenzothiophene, perhydrobenzothiophene, dihydroisobenzothiophene,perhydroisobenzothiophene, dihydroindazole, perhydroindazole,dihydroquinoline, tetrahydroquinoline, perhydroquinoline,dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline,dihydrophthalazine, tetrahydrophthalazine, perhydrophthatazine,dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine,dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline,dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline,dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline,dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole,perhydrobenzothiazole, dihydrobenzoimidazole, perhydrobenzoimidazole,benzooxazepine, benzooxadiazepine, benzothiazepine, benzodithiazepine,benzoazepine, benzodiazepine, indolooxoazepine,indolotetrahydrooxazepine, indolooxadiazepine,indolotetrahydrooxadiazepine, indolothiazepine,indolotetrahydrothiazepine, indolothiadiazepine,indolotetrahydrothiadiazepine, indoloazepine, indolotetrahydroazepine,indolodiazepine, indolotetrahydrodiazepine, benzofurazan,benzothiadiazole, benzotriazole, camphere, imidazothiazole ring etc.

In formula (I), hetero ring represented by R² and R³, taken togetherbonded to nitrogen atom, and R²⁸ and R²⁹, taken together bonded tonitrogen atom, means a 5-7 membered mono-cyclic hetero ring containing1-2 nitrogen atoms, one oxygen atom or one sulfur atom. For example, a5-7 membered mono-cyclic hetero ring containing 1-2 nitrogen atoms, oneoxygen atom or one sulfur atom includes pyrroline pyrrolidine,imidazoline, imidazolidine, pyrazoline, pyrazolidine, piperidine,piperazine, piperidine, piperazine, morpholine, thiomorpholine,tetrahydropyrimidine, tetrahydropyridazine ring etc.

In formula (I),

represented by AA¹ may be an α-amino acid residue. For example, glycine,alanine, serine, threonine, cystine, valine, methionine, leucine,isoleucine, phenylalanine, tyrosine, tryptophan, aspartic acid, glutamicacid, arginine, glutamine, lysine, histidine etc.

In formula (I),

represented by AA² may be an α-amino acid residue. For example, glycine,alanine, serine, threonine, cystine, valine, methionine, leucine,isoleucine, phenylalanine, tyrosine, tryptophan, aspartic acid, glutamicacid, arginine, glutamine, lysine, histidine, proline etc.

In formula (I), C1-4 alkyl di-substituted by phenyl represented by —Z—Emeans methyl, ethyl, propyl, butyl and the isomer thereof, which aredisubstituted by phenyl group.

In formula (I), keto group represented by substituent of Cyc¹ may besubstituted at one carbon atom, one nitrogen atom, or one or two sulfaratom.

In the present invention, non-toxic salts includes all such salts. Forexample, the following salt, acid addition salt or hydrate, etc.

Salt

The compounds of formula (I) of the present invention in the case offree carboxylic acid or tetrazole may be converted into a correspondingnon-toxic salt by methods known per se. Non toxic and water-solublesalts are preferable. Suitable salts, for example, are salts of analkaline metal (potassium, sodium etc.), salts of an alkaline earthmetal (calcium, magnesium etc.), ammonium salts and salts ofpharmaceutically-acceptable organic amines (tetramethylammonium,triethylamine, methylamine, dimethylamine, cyclopentylamine,benzylamine, phenethylamine, piperidine, monoethanolamine,diethanolamine, tris(hydroxymethyl)amine, lysine, arginine,N-methyl-D-glucamine etc.).

Acid Additional Salt

The compounds of formula (I) of the present invention may be convertedinto a corresponding acid addition salt by methods known per se. Nontoxic and water-soluble salts are preferable. Suitable acid additionsalts include salts of inorganic acids such as hydrochloric acid,hydrobromic acid, sulfuric acid, phosphoric acid and nitric acid, andsalts with organic acids such as acetic acid, trifluoroacetic acid,lactic acid, tartaric acid, oxalic acid, fumaric acid, maleic acid,benzenesulfonic acid, toluenesulfonic acid, isethionic acid, glucuronicacid and gluconic acid.

Hydrate

The compounds of formula (I) or salts thereof of the present inventionmay be converted into a corresponding hydrate by methods known per se.

Preferred compounds of the present invention are as follows: tetrazolederivative of formula I (1)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (2)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (3)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (4)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (5)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (6)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (7)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (8)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (9)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (10)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (11)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (12)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (13)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (14)

(wherein R⁴, R⁹ and R¹⁰ have the same meaning as hereinbefore defined),the compound of formula I (15)

(wherein R⁴ R⁹ and R¹⁰ have the same meaning as hereinbefore defined),the compound of formula I (16)

(wherein R⁴, R⁹ and R¹⁰ have the same meaning as hereinbefore defined),the compound of formula i (17)

(wherein R⁴, R⁹ and R¹⁰ have the same meaning as hereinbefore defined),the compound of formula I (18)

(wherein R⁴, R⁹ and R¹⁰ have the same meaning as hereinbefore defined),the compound of formula I (19)

(wherein R⁴, R⁹ and R¹⁰ have the same meaning as hereinbefore defined),the compound of formula I (20)

(wherein R¹⁵, R¹⁶, R¹⁷ and —(CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (21)

(wherein R¹⁵, R¹⁶, R¹⁷ and (CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (22)

(wherein R¹⁵, R¹⁶, R¹⁷ and —(CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (23)

(wherein R¹⁵, R¹⁶, R¹⁷ and —(CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (24)

(wherein R¹⁵, R¹⁶, R¹⁷ and —(CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (25)

(wherein R¹⁵, R¹⁶, R¹⁷ and —(CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (26)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (27)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (28)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (29)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (30)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (31)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (32)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (33)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (34)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (35)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (36)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (37)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (38)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (39)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (40)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (41)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (42)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (43)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (44)

(wherein R⁴, R⁹ and R₁₀ have the same meaning as hereinbefore defined),the compound of formula I (45)

(wherein R⁴, R⁹ and R¹⁰ have the same meaning as hereinbefore defined),the compound of formula I (46)

(wherein R⁴, R⁹ and R¹⁰ have the same meaning as hereinbefore defined),the compound of formula I (47)

(wherein R⁴, R⁹ and R¹⁰ have the same meaning as hereinbefore defined),the compound formula I (48)

(wherein R¹⁵, R¹⁶, R¹⁷ and —(CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (49)

(wherein R¹⁵, R¹⁶, R¹⁷ and —(CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (50)

(wherein R¹⁵, R¹⁶, R¹⁷ and —(CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (51)

(wherein R¹⁵, R¹⁶, R¹⁷ and —(CH₂)_(q)— have the same meaning ashereinbefore defined), the compound of formula I (52)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (53)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (54)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (55)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (56)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (57)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (58)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (59)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (60)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (61)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (62)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (63)

(wherein Y has the same meaning as hereinbefore defined), the compoundof formula I (64)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (65)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (66)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (67)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (68)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (69)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (70)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (71)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (72)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (73)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (74)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (75)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (76)

(wherein R¹ has the same meaning as hereinbefore defined), the compoundof formula I (77)

(wherein R¹ has the same meaning as hereinbefore defined) or a non-toxicsalt thereof, an acid addition salt thereof or a hydrate thereof.

Examples of representative compounds of formula (I) of the presentinvention are listed in Table 1-77 or a non-toxic salt thereof, an acidaddition salt thereof or a hydrate thereof and described in example.

TABLE 1 I (1)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 2 I (2)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 3 I (3)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 4 I (4)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 5 I (5)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 6 I (6)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 7 I (7)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 8 I (8)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 9 I (9)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 10 I (10)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 11 I (11)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 12 I (12)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 13 I (13)

No. Y 1

2

3

4

5

6

7

8

9

10 

TABLE 14 I (14)

No. R⁴ R⁹ R¹⁰ 1 i-Pr H

2 i-Pr H —CH₂—OH 3 i-Pr H

4 i-Pr Me Me 5 i-Pr —(CH₂)₃— 6 i-Pr —CH₂CH═CHCH₂— 7 Me H Me 8 i-Bu H Me9

H Me 10 

H Me 11 

H Me 12 

H Me

TABLE 15 I (15)

No. R⁴ R⁹ R¹⁰ 1 i-Pr H

2 i-Pr H —CH₂—OH 3 i-Pr H

4 i-Pr Me Me 5 i-Pr —(CH₂)₃— 6 i-Pr —CH₂CH═CHCH₂— 7 Me H Me 8 i-Bu H Me9

H Me 10 

H Me 11 

H Me 12 

H Me

TABLE 16 I(16)

No. R⁴ R⁹ R¹⁰ 1 i-Pr H

2 i-Pr H —CH₂—OH 3 i-Pr H

4 i-Pr Me Me 5 i-Pr —(CH₂)₃— 6 i-Pr —CH₂CH═CHCH₂— 7 Me H Me 8 i-Bu H Me9

H Me 10

H Me 11

H Me 12

H Me

TABLE 17 I(17)

No. R⁴ R⁹ R¹⁰ 1 i-Pr H

2 i-Pr H —CH₂—OH 3 i-Pr H

4 i-Pr Me Me 5 i-Pr —(CH₂)₃— 6 i-Pr —CH₂CH═CHCH₂— 7 Me H Me 8 i-Bu H Me9

H Me 10

H Me 11

H Me 12

H Me

TABLE 18 I(18)

No. R⁴ R⁹ R¹⁰ 1 i-Pr H

2 i-Pr H —CH₂—OH 3 i-Pr H

4 i-Pr Me Me 5 i-Pr —(CH₂)₃— 6 i-Pr —CH₂CH═CHCH₂— 7 Me H Me 8 i-Bu H Me9

H Me 10

H Me 11

H Me 12

H Me

TABLE 19 I(19)

No. R⁴ R⁹ R¹⁰ 1 i-Pr H

2 i-Pr H —CH₂—OH 3 i-Pr H

4 i-Pr Me Me 5 i-Pr —(CH₂)₃— 6 i-Pr —CH₂CH═CHCH₂— 7 Me H Me 8 i-Bu H Me9

H Me 10

H Me 11

H Me 12

H Me

TABLE 20 I(20)

No.

R¹⁷ 1

Me 2

Me 3

Me 4

Me 5

Me 6

Me 7

Me 8

Me 9

Me 10

Me 11

Me 12

Me

TABLE 21 I(21)

No.

R¹⁷ 1

Me 2

Me 3

Me 4

Me 5

Me 6

Me 7

Me 8

Me 9

Me 10

Me 11

Me 12

Me

TABLE 22 I(22)

No.

R¹⁷ 1

Me 2

Me 3

Me 4

Me 5

Me 6

Me 7

Me 8

Me 9

Me 10

Me 11

Me 12

Me

TABLE 23 I(23)

No.

R¹⁷ 1

Me 2

Me 3

Me 4

Me 5

Me 6

Me 7

Me 8

Me 9

Me 10

Me 11

Me 12

Me

TABLE 24 I(24)

No.

R¹⁷ 1

Me 2

Me 3

Me 4

Me 5

Me 6

Me 7

Me 8

Me 9

Me 10

Me 11

Me 12

Me

TABLE 25 I(25)

No.

R¹⁷ 1

Me 2

Me 3

Me 4

Me 5

Me 6

Me 7

Me 8

Me 9

Me 10

Me 11

Me 12

Me

TABLE 26 I(26)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 27 I(27)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 28 I(28)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 29 I(29)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 30 I(30)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 31 I (31)

No. R¹  1 Me  2

 3

 4

 5

 6

 7

 8

 9

10

11

12

13

14

15

16

17

18

TABLE 32 I (32)

No. R¹  1 Me  2

 3

 4

 5

 6

 7

 8

 9

10

11

12

13

14

15

16

17

18

TABLE 33 I (33)

No. R¹  1 Me  2

 3

 4

 5

 6

 7

 8

 9

10

11

12

13

14

15

16

17

18

TABLE 34 I (34)

No. R¹  1 Me  2

 3

 4

 5

 6

 7

 8

 9

10

11

12

13

14

15

16

17

18

TABLE 35 I (35)

No. R¹  1 Me  2

 3

 4

 5

 6

 7

 8

 9

10

11

12

13

14

15

16

17

18

TABLE 36 I (36)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 37 I (37)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 38 I (38)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 39 I (39)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 40 I (40)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 41 I (41)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 42 I (42)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 43 I (43)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 44 I (44)

No. R⁴ R⁹ R¹⁰  1 i-Pr H

 2 i-Pr H —CH₂—OH  3 i-Pr H

 4 i-Pr Me Me  5 i-Pr —(CH₂)₃—  6 i-Pr —CH₂CH═CHCH₂—  7 Me H Me  8 i-BuH Me  9

H Me 10

H Me 11

H Me 12

H Me

TABLE 45 I (45)

No. R⁴ R⁹ R¹⁰  1 i-Pr H

 2 i-Pr H —CH₂—OH  3 i-Pr H

 4 i-Pr Me Me  5 i-Pr —(CH₂)₃—  6 i-Pr —CH₂CH═CHCH₂—  7 Me H Me  8 i-BuH Me  9

H Me 10

H Me 11

H Me 12

H Me

TABLE 46 I (46)

No. R⁴ R⁹ R¹⁰  1 i-Pr H

 2 i-Pr H —CH₂—OH  3 i-Pr H

 4 i-Pr Me Me  5 i-Pr —(CH₂)₃—  6 i-Pr —CH₂CH═CHCH₂—  7 Me H Me  8 i-BuH Me  9

H Me 10

H Me 11

H Me 12

H Me

TABLE 47 I (47)

No. R⁴ R⁹ R¹⁰  1 i-Pr H

 2 i-Pr H —CH₂—OH  3 i-Pr H

 4 i-Pr Me Me  5 i-Pr —(CH₂)₃—  6 i-Pr —CH₂CH═CHCH₂—  7 Me H Me  8 i-BuH Me  9

H Me 10

H Me 11

H Me 12

H Me

TABLE 48 I (48)

No.

R¹⁷  1

Me  2

Me  3

Me  4

Me  5

Me  6

Me  7

Me  8

Me  9

Me 10

Me 11

Me 12

Me

TABLE 49 I (49)

No.

R¹⁷  1

Me  2

Me  3

Me  4

Me  5

Me  6

Me  7

Me  8

Me  9

Me 10

Me 11

Me 12

Me

TABLE 50 I (50)

No.

R¹⁷  1

Me  2

Me  3

Me  4

Me  5

Me  6

Me  7

Me  8

Me  9

Me 10

Me 11

Me 12

Me

TABLE 51 I (51)

No.

R¹⁷  1

Me  2

Me  3

Me  4

Me  5

Me  6

Me  7

Me  8

Me  9

Me 10

Me 11

Me 12

Me

TABLE 52 I (52)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 53 I (53)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 54 I (54)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 55 I (55)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 56 I (56)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 57 I (57)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 58 I (58)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 59 I (59)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 60 I (60)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 61 I (61)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 62 I (62)

No. Y  1

 2

 3

 4

 5

 6

 7

 8

 9

10

TABLE 63 I(63)

No. Y 1

2

3

4

5

6

7

8

9

10

TABLE 64 I(64)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 65 I(65)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 66 I(66)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 67 I(67)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 68 I(68)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 69 I(69)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 70 I(70)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 71 I(71)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 72 I(72)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 73 I(73)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 74 I(74)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 75 I(75)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 76 I(76)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

TABLE 77 I(77)

No. R¹ No. R¹ 1 Me 10

2

11

3

12

4

13

5

14

6

15

7

16

8

17

9

18

Processes for the Preparation

For compounds of formula (I) of the present invention, those in which Rdoes not contain a COOH group, AA¹ does not contain a COOH group, AA²does not contain a COOH group and Y does not contain a COOH group, i.e.,the compounds of formula (I-A)

wherein R^(A), AA^(1A), AA^(2A) and Y^(A) have the same meaning ashereinbefore defined for R, AA¹, AA² and Y, respectively, provided thatall of R^(A), AA^(1A), AA^(2A) and Y^(A) do not contain a COOH group maybe prepared by methods (a) to (b) as follows.

(a) For compounds of formula (I-A) of the present invention, those inwhich R^(A) does not contain an amino group, AA^(1A) does not contain anamino group, AA^(2A) does not contain an amino group, Y^(A) does notcontain an amino group and —Z—E group is bonded directly to a carbonatom of tetrazole of Y^(A),i.e., the compounds of formula (I-A-a)

wherein R^(A-a), AA^(1A-a), AA^(2A-a) and Y^(A-a) have the same meaningas hereinbefore defined for R^(A), AA^(1A), AA^(2A) and Y^(A)respectively, provided that all of R^(A-a), AA^(1A-a), AA^(2A-a) andY^(A-a) do not contain an amino group and —Z—E group is bonded directlyto a carbon atom of tetrazole of Y^(A-a) may be prepared by methods(a-1), (a-2), (a-3) or (a-4) as follows.

(a-1) For compounds of formula (I-A-a) of the present invention, thosein which —Z—E do not tri(C1-4 alkyl)silyl, i.e., the compounds offormula (I-A-a-1)

wherein Y^(A-a-1) have the same meaning as hereinbefore defined forY^(A-a), provided that of Y^(A-a-1) do not tri(C1-4 alkyl)silyl, theother symbols are the same meaning as hereinbefore defined may beprepared by reacting a compound of formula (II-a-1)

wherein R^(19A) is C1-8 alkyl, phenyl or C1-4 alkyl substituted withphenyl, X^(A-a-1) is a leaving group known per se (e.g., chlorine,bromine or iodine atom, mesyl, tosyl group etc.) and the other symbolshave the same meaning as hereinbefore defined with a compound of formula(III-a-1)

wherein Z^(A-a-1) and E^(A-a-1) has the same meaning as hereinbeforedefined for Z and E, provided that —Z^(A-a-1)—E^(A-a-1) do not containCOOH, amino groups and tri(C1-4 alkyl)silyl group.

This reaction is known per se, and may be carried out, for example, inan organic solvent (e.g., N,N-dimethylformamide etc.), in the presenceof potassium fluoride etc., at a temperature of from 20° C. to 40° C.

(a-2) For compounds of formula (I-A-a) of the present invention, thosein which —Z—E represent tri(C1-4 alkyl)silyl, i.e., the compounds offormula (I-A-a-2)

wherein Y^(A-a-2) have the same meaning as hereinbefore defined forY^(A-a), provided that of —Z—E group in Y^(A-a-2) represent tri(C1-4alkyl)silyl, the other symbols are the same meaning as hereinbeforedefined may be prepared by reacting a compound of formula (II-a-2)

wherein G is C1-4 alkyl and the other symbols have the same meaning ashereinbefore defined with a compound of formula (III-a-2)

wherein R^(III-a-2-1), R^(III-a-2-2) and R^(III-a-2-3) is eachindependently C1-4 alkyl.

This reaction is known per se, and may be carried out, for example, thesame method described in Chem. Pharm. Bull., 30, 3450-3452 (1982). Forexample, this reaction carried out by reacting the compound of theformula (III-a-2) with alkylaminolithium (e.g., lithium diisobutylamide[LDA], etc.) in an inert organic solvent (e.g., diethyl ether,tetrahydrofuran etc.) under an atomoshere inert gas (e.g., argon,nitrogen, etc.) at a temperature of from −20° C. to 0° C., and then byreacting the obtained lithium compound with the compound of the formula(II-a-2) at a temperature of from −20° C. to 0° C.

(a-3) For compounds of formula (I-A-a) of the present invention, thosein which R^(A-a) and NH group in AA^(1A-a) or AA^(2A-a) bonded to formamide bond, sulfonamide bond or sulfonylurea bond, i.e., the compoundsof formula (I-A-a-3)

wherein R^(A-a-3), AA^(1A-a-3) and AA^(2A-a-3) have the same meaning ashereinbefore defined for R^(A-a), AA^(1A-a) and AA^(2A-a), provided thatof R^(A-a-3) and NH group in AA^(1A-a-3), AA^(2A-a-3) and Y^(A-a) bondedto form amide bond, sulfonamide bond or sulfonylurea bond, the othersymbols are the same meaning as hereinbefore defined may be prepared byreacting a compound of formula (II-a-3)

wherein X^(A-a-3) is a leaving group (e.g., chlorine, bromine or iodineatom etc.) or a hydroxy group and the other symbols have the samemeaning as hereinbefore defined with a compound of formula (III-a-3)

H₂N—Y^(A-a)  (III-a-3)

wherein all the symbols have the same meaning as hereinbefore defined.

The reaction can be carried out as an amidation reaction,sulfonamidation reaction, sulfonylurea reaction and the like.

Amidation reactions are known per se and can be carried out by, forexample:

(1) using an acid halide,

(2) using a mixed acid anhydride,

(3) using a condensing agent etc.

Each of those methods can be carried out, for example, as follows:

(1) the method using an acid halide may be carried out, for example, byreacting a carboxylic acid with an acid halide (e.g., oxalyl chloride,thionyl chloride etc.) in an inert organic solvent (e.g., chloroform,methylene chloride, diethyl ether, tetrahydrofuran etc.) or without asolvent at from −20° C. to the reflux temperature of the solvent, andthen by reacting the acid halide obtained with an amine in the presenceof a tertiary amine (e.g., pyridine, triethylamine, dimethylaniline,dimethylaminopyridine etc.) in an inert organic solvent (e.g.,chloroform, methylene chloride, diethyl ether, tetrahydrofuran etc.), ata temperature of from 0° C. to 40° C.,

(2) the method using a mixed acid anhydride may be carried out, forexample, by reacting a carboxylic acid and an acid halide (e.g.,pivaloyl chloride, tosyl chloride, mesyl chloride etc.) or an acidderivative (e.g., ethyl chloroformate, isobutyl chloroformate etc.) inthe presence of a tertiary amine (e.g., pyridine, triethylamine,dimethylaniline, dimethylaminopyridine etc.) in an inert organic solvent(e.g., chloroform, methylene chloride, diethyl ether, tetrahydrofuranetc.) or without a solvent at a temperature of from 0° C. to 40° C., andthen by reacting the mixture of acid anhydride obtained with an amine inan inert organic solvent (e.g., chloroform, methylene chloride, diethylether, tetrahydrofuran etc.), at a temperature of from 0° C. to 40° C.,or

(3) the method using a condensing agent (e.g., 1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide(EDC), 2-chloro-1-methylpyridinium iodide etc.) may be carried out, forexample, by reacting a carboxylic acid with an amine using a condensingagent in the presence or absence of a tertiary amine (e.g., pyridine,triethylamine, dimethylaniline, dimethylaminopyridine etc.) in an inertorganic solvent (e.g., chloroform, methylene chloride, dimethylformamide, diethyl ether etc.) or without a solvent at a temperature offrom 0° C. to 40° C.

The reactions (1), (2) and (3) hereinbefore described preferably may becarried out in an atmosphere of inert gas (e.g., argon, nitrogen etc.)under anhydrous conditions.

Sulfonamidation reactions are known pre se, and can be carried out, forexample, by reacting a sulfonic acid derivatives with an acid halide(e.g., oxalyl chloride, thionyl chloride, phosphous trichloride,phosphous pentachloride etc.) in an inert organic solvent (e.g.,chloroform, methylene chloride, diethyl ether, tetrahydrofuran etc.) orwithout a solvent at from −20° C. to the reflux temperature of thesolvent, and then by reacting the sulfonyl halide obtained with an aminein the presence of a tertiary amine (e.g., pyridine, triethylamine,dimethylaniline, dimethylaminopyridine etc.) in an inert organic solvent(e.g., chloroform, methylene chloride, diethyl ether, tetrahydrofuranetc.), at a temperature of from 0° C. to 40° C.

Formation of sulfonylurea reactions are known pre se, and can be carriedout, for example, by reacting a aminosulfonic acid derivatives with anacid halide (e.g., oxalyl chloride, thionyl chloride, phosphoustrichloride, phosphous pentachloride etc.) in an inert organic solvent(e.g., chloroform, methylene chloride, diethyl ether, tetrahydrofuranetc.) or without a solvent at from −20° C. to the reflux temperature ofthe solvent, and then by reacting the aminosulfonyl halide obtained withan amine in the presence of a tertiary amine (e.g., pyridine,triethylamine, dimethylaniline, dimethylaminopyridine etc.) in an inertorganic solvent (e.g., chloroform, methylene chloride, diethyl ether,tetrahydrofuran etc.), at a temperature of from 0° C. to 40° C.

(a-3) For compounds-of formula (I-A-a) of the present invention, thosein which R^(A-a) and NH group in AA^(1A-a) or AA^(2A-a) bonded to formurea bond, i.e., the compounds of formula (I-A-a-4)

wherein R^(1A-a-3), J^(A-a-4), AA^(1A-a-4) and AA^(2A-a-4) have the samemeaning as hereinbefore defined for R¹, J, AA^(1A-a) and AA^(2A-a),provided that of R^(1A-a-4)—J^(A-a-4) group do not contain an COOH,amino group, and carbonyl bonded to NH group in R^(1A-a-4)—J^(A-a-4),the other symbols are the same meaning as hereinbefore defined may beprepared by reacting a compound of formula (II-a-4)

wherein all the symbols have the same meaning as hereinbefore definedwith a compound of formula (III-a-4)

R^(1A-a-4)—J^(A-a-4)—H  (III-a-4)

wherein all the symbols have the same meaning as hereinbefore defined.

Formation of urea reactions are known pre se, and can be carried out,for example, in an inert organic solvent (e.g., dimethylformamide,dichloromethane, tetrahydrofuran etc.), using N,N′-carbodiimidazole, anamine in the presence or absence of a tertiary amine (e.g., pyridine,triethylamine, dimethylaniline, dimethylaminopyridine etc.), at atemperature of from 0° C. to 80° C.

(b) For compounds of formula (I-A) of the present invention, those inwhich at least one of R^(A), AA^(1A), AA^(2A) and Y^(A) representcontains an amino group i.e., the compounds of formula (I-A-b)

wherein R^(A-b), AA^(1A-b), AA^(2A-b) and Y^(A-b) have the same meaningas hereinbefore defined for R^(A), AA^(1A), AA^(2A) and Y^(A),respectively, provided that at least one of R^(A-b), AA^(1A-b),AA^(2A-b) and Y^(A-b) represent contains an amino group may be preparedby methods (b-1) or (b-2) as follows.

(b-1) For compounds of formula (I-A-b) of the present invention may beprepared by subjecting the amino protecting group to elimination, thecompound prepared by the same methods (a-1), (a-2), (a-3) or (a-4) aboveand protecting an amino group as known per se (e.g., t-butyloxycarbonyl,benzyloxycarbonyl, triphenylmethyl, 2-(trimethylsilyl)ethoxymethyl ortrifluoroacetyl etc.), i.e., the compound of formula (II-b-1)

wherein R^(A-IIb-1), AA^(1A-IIb-1), AA^(2A-IIb-1) and Y^(A-IIb-1) havethe same meaning as hereinbefore defined for R^(A-b), AA^(1A-b),AA^(2A-b) and Y^(A-b) respectively, provided that at least one ofR^(A-IIb-1), AA^(1A-IIb-1), AA^(2A-IIb-1) and Y^(A-IIb-1) representcontains a protected amino group with a known protecting group (e.g.,t-butyloxycarbonyl, benzyloxycarbonyl, triphenylmethyl,2-(trimethylsilyl) ethoxymethyl or trifluoroacetyl etc.).

The elimination of an amino protecting group May be carried out bymethods known per se, and depends on the protecting group. For example,when the protecting group is t-butoxycarbonyl, triphenylmethyl or2-(trimethylsilyl)ethoxymethyl, the reaction may be carried out in awater-miscible organic solvent (e.g., methanol, tetrahydrofuran,dioxane, acetone etc.) in the presence of aqueous solution of organicacid (e.g., acetic acid, trifluoroacetic acid etc.) or inorganic acid(hydrochloric acid, sulfuric acid etc.) or a mixture of them, at atemperature of from 0° C. to 100° C.

When the protecting group is a benzyloxycarbonyl group, the eliminationof the protecting group can be carried out by hydrogenation. Thehydrogenation reaction is known per se, and may be carried out, forexample, in an inert solvent [ether (e.g., tetrahydrofuran, dioxane,diethoxyethane, diethyl ether etc.), alcohol (e.g., methanol, ethanoletc.), benzene analogues (e.g., benzene, toluene etc.), ketone (e.g.,acetone, methyl ethyl ketone etc.), nitrile (e.g., acetonitrile etc.),amide (e.g., dimethylformamide etc.), water, ethyl acetate, acetic acid,mixture of two or more of them etc.], in the presence of a catalyst ofhydrogenation (e.g., palladium on activated carbon, palladium black,palladium, palladium hydroxide on carbon, platinum oxide, nickel, Raneynickel (registered trade mark) etc.), in the presence or absence of aninorganic acid (e.g., hydrochloric acid, sulfuric acid, hypochlorousacid, boric acid, tetrafluoroboric acid etc.) or an organic acid (e.g.,acetic acid, p-toluenesulfonic acid, oxalic acid, trifluoroacetic acid,formic acid etc.), at ordinary or additional pressure under anatmosphere of hydrogen, at a temperature of from 0° C. to 200° C. Whenusing an acid, its salt may be used at the same time.

Furthermore, when the protecting group is a trifluoroacetyl group, maybe carried out, for example, in a water-miscible organic solvent (e.g.,methanol, tetrahydrofuran, dioxan, acetone etc.), using a hydroxide ofan alkali metal (e.g., sodium hydroxide, potassium hydroxide, etc.),hydroxide of an alkaline earth metal (e.g., barium hydroxide, calciumhydroxide, etc.), or a carbonate of an alkali metal (e.g., sodiumcarbonate, potassium carbonate, etc.), or aqueous solution thereof, at atemperature of from 0° C. to 40° C.

It should be easily understood by those skilled in the art, that otheramino protecting groups that can be used in the present invention areavailable and the choices are not limited only to t-butyloxycarbonyl,benzyloxycarbonyl, triphenylmethyl, 2-(trimethylsilyl) ethoxymethyl ortrifluoroacetyl groups. Any group which can be easily and selectivelyeliminated essentially can be used. For example, a protecting group maybe one described in Protective Groups in Organic Synthesis (T. W.Greene, Wiley, New York (1991)). The proposed compounds of the presentinvention may be easily prepared with those protecting group practicingknown methods.

(b-2) For compounds of formula (I-A-b) of the present invention may beprepared by subjecting reduction, the compound prepared by the samemethods (a-1), (a-2), (a-3) or (a-4) above and having nitro group, i.e.,the compound of formula (II-b-2)

wherein R^(A-IIb-2), AA^(1A-IIb-2), AA^(2A-IIb-2) and Y^(A-IIb-2) havethe same meaning as hereinbefore defined for R^(A-b), AA^(1A-b),AA^(2A-b) and Y^(a-b), respectively, provided that at least one ofR^(A-IIb-2), AA^(1A-IIb-2), AA^(2A-IIb-2) and Y^(A-IIb-2) contains anitro group.

Reduction of nitro group is known per se, and may be carried out,hydrogenation or reduction by using organic metal.

Hydrogenation may be carried out by the same method as hereinbeforedescribed.

Reduction by using organic metal is known per se, and may be carriedout, for example, in a water-miscible organic solvent (e.g., ethanol,methanol etc.), in the presence or absence of an aqueous solution ofhydrochloric acid, by using organic metal (e.g., zinc, iron, tin, tinchloride, iron chloride, etc.), at a temperature of from 50° C. to 150°C.

For compounds of formula (I) of the present invention, those in which atleast one of R, AA¹, AA² and Y represent contain a COOH group, i.e., thecompounds of formula (I-B)

wherein R^(B), AA^(1B), AA^(2B) and Y^(B) have the same meaning ashereinbefore defined for R, AA¹, AA² and Y, respectively, provided thatat least one of R^(B), AA^(1B), AA^(2B) and Y^(B) represent contains aCOOH group may be prepared by, for example, hydrolysis of at-butylester, hydrogenation, hydrolysis of an ester or a cleavagereaction of a 2,2,2-trichloroethylester group of a compound having atleast one COOH group derivatized to contain a t-butylester, benzylester,alkylester or 2,2,2-trichloroethylester i.e., the compound of formula(I-A-1)

wherein R^(A-1), AA^(1A-1), AA^(2A-1) and Y^(A-1) have the same meaningas hereinbefore defined for R^(A), AA^(1A), AA^(2A) and Y^(A),respectively, provided that at least one of R^(A-1), AA^(1A-1),AA^(2A-1) and Y^(A-1) represent contains a t-butylester, benzylester,alkylester or 2,2,2-trichloroethylester group.

Hydrolysis of t-butylester is known per se, and may be carried out, forexample, in an inert organic solvent (e.g., dichloromethane, chloroform,methanol, dioxane, ethyl acetate, anisole etc.) in the presence of anorganic acid (e.g., trifluoroacetic acid etc.), or inorganic acid (e.g.,hydrochloric acid etc.) or a mixture of them, at a temperature of from0° C. to 90° C.

Hydrogenation may be carried out by the same method as hereinbeforedescribed.

Hydrolysis of an ester is known per se, and may be carried out, forexample, by hydrolysis in acid or under alkaline conditions. Hydrolysisunder alkaline conditions may be carried out, for example, in anappropriate organic solvent (e.g., methanol, dimethoxyethane etc.),using a hydroxide or a carbonate of an alkali metal or alkaline earthmetal, at a temperature of from 0° C. to 40° C. Hydrolysis under acidicconditions may be carried out by the same method as for hydrolysis of at-butylester.

Cleavage of 2,2,2-trichloroethylester is known per se, and may becarried out, for example, in an acidic solvent (e.g., acetic acid,buffer of pH4.2-7.2 or a mixture of organic solvent (e.g.tetrahydrofuran etc.) and solution thereof etc.), in the presence ofzinc powder, sonicated or not sonicated, at a temperature of from 0° C.to 40° C.

It should be easily understood by those skilled in the art that thecarboxyl protecting group of the present invention are not to onlyt-butylester, benzylester or 2,2,2-trichloroethylester but any groupwhich can be easily and selectively eliminated can be used in thepresent invention. For example, a protecting group described inProtective Groups in Organic Synthesis (T. W. Greene, Wiley, N.Y.(1991)) may be used. The proposed compounds of the present invention maybe easily prepared using those protecting groups and practicing knownmethods.

For compounds of formula (I) of the present invention, those in which Rdoes not contain a COOH and amino group, AA¹ does not contain a COOH andamino group, AA² does not contain a COOH and amino group, Y does notcontain a COOH and amino group and Z or R²⁰ group in Y represent amidegroup, i.e., the compounds of formula (I-C)

wherein R^(C), AA^(1C), AA^(2C) and Y^(C) have the same meaning ashereinbefore defined for R, AA¹, AA² and Y, respectively, provided thatall of R^(C), AA^(1C), AA^(2C) and Y^(C) do not contain a COOH and aminogroup, and Z or R²⁰ group in Y^(C) represent amide group may be preparedby subjecting the amidation, the compound prepared by the same methods(I-B) above and Z or R²⁰ selectively represent —COOH, methylester orethylester, i.e., the compound of formula (I-B-1)

wherein Y^(C-B-1) has the same meaning as hereinbefore defined forY^(C), provided that Z or R²⁰ in Y^(c) represent COOH with an aminecompound of formula (III-C-1)

wherein all the symbols are the same meaning as hereinbefore defined.

Amidation of —COOH group and amine may be carried out by the same methodas hereinbefore described.

Amidation of -methylester or ethylester and amine may be carried out,for example, in a water-miscible organic solvent (e.g., methanol,ethanol etc.), an aqueous solution of an amine compound of the formula(III-C-1), at room temperature.

For compounds of formula (I) of the present invention, those in which atleast one of R, AA¹, AA² and Y represent contain a COOH and amino groupand Z or R²⁰ group in Y represent amide group, may be prepared bysubjecting the amino protecting group to elimination hereinbeforedescribed or the carboxy protecting group to elimination hereinbeforedescribed, the compound prepared by the same methods (I-C) above.

A compound of formula (II-a-1) may be prepared by methods known per se.For example, the compound may be produced by methods described in theliterature of J. Med. Chem., 37, 563 (1994) or in EP 0623592.

The products of such synthesis reactions may be purified in aconventional manner. For example, it may be carried out by distillationat atmospheric or reduced pressure, high performance liquidchromatography, thin layer chromatography or column chromatography usingsilica gel or magnesium silicate, washing or recrystallization.Purification may be carried out after each reaction, or after a seriesof reactions.

The starting materials and each reagents used in the process for thepreparation of the present invention are known per se or may be easilyprepared by known methods.

Effect

It has been confirmed that the compounds of formula (I) of the presentinvention have inhibitory activities on IL-1β converting enzyme. Forexample, in laboratory tests the following results were obtained.

Method

(1) Assay for IL-1β converting enzyme

The reaction mixture contains, for example, 20 mM of HEPES-NaOH pH7.4,10 mM of KOH, 1.5 mM of MgCl₂, 0.1 mM of EDTA and 10% glycerol. Variousconcentrations of test compounds (50 μl), human ICE solution (50 μl) andvarious concentrations of substrate (Ac-Tyr-Val-Ala-Asp-MCA) were mixedand incubated at 37° C. Fluorescence intensity was measured at En=355 nmand Ex=460 nm. The compounds of the present invention have ICEinhibitory values less than 1 μM (for example, in Example 2(1), thecompound has an IC₅₀ of 0.03 μM).

In the aboved example method,

HEPES is 4-(2-Hydroxyethyl)-1-piperazineethane-sulfonic acid,

EDTA is Ethylenediamine tetraacetate, and

Ac-Tyr-Val-Ala-Asp-MCA isAcetyl-L-tyrosyl-L-valyl-L-alanyl-L-asparaginic acid4-methyl-coumarinyl-7-amide.

Toxicity

The compounds of the present invention are substantially non-toxic.Therefore, the compounds of the present invention may be consideredsufficiently safe and suitable for pharmaceutical use.

Application for Pharmaceuticals

Compounds of the present invention have an inhibitory activity on ICE inanimals, including humans. Therefore the compounds are useful forprevention and/or treatment of insulin dependent diabetes (type I),multiple sclerosis, acute or delayed type hypersensitivity, infectiousdiseases, infection complications, septic shock, arthritis, colitis,glomerular nephritis, hepatitis, hepatic cirrhosis, pancreatitis,reperfusion injury, cholangeitis, encephalitis, endocarditis,myocarditis, vasculitis, Alzheimer's disease, Parkinson's disease,dementia, cerebral vascular disturbance, neuro-degenerative diseases,bone or cartilage-resorption diseases, AIDS, ARC (AIDS related complex),adult T cell leukemia, hairy cell (pilocytic) leukemia, myelosis,respiratory dysfunction, arthropathy, uveitis, neoplasm, diffusecollagen diseases such as systemic lupus erythematosis or rheumatoidarthritis, ulcerative colitis, Sjogren's syndrome, primary biliarycirrhosis, idiopathic thrombocytopnic purpura, autoimmonohaemolyticanemia, severe myasthenia, osteodisplasia syndrome, periodicthrombocytopenia, aplastic anemia, idiopathic thrombocytopenia, variousdiseases accompanied with thrombocytopenia such as disseminatedintravascular coagulation, adult dyspnea syndrome, hyperplasia of theprostae gland, myoma of the uterus, asthma bronchiole, arteriosclerosis,various kinds of teratoma, nephritis, senile cataract, chronic fatiguesyndrome, myodystrophy, peripheral nervous disturbance, Crohn's diseasesand osteo arthritics etc. essentially disorders arising from orinfluenced by IL-1β activity.

For the purpose above described, the compounds of formula (I) of thepresent invention, non-toxic salts thereof, acid additional saltsthereof and hydrates thereof may be normally administered systemicallyor partially, usually by oral or parenteral administration.

The doses to be administered are determined depending on age, bodyweight, symptom, the -desired therapeutic effect, the route ofadministration, the duration of the treatment etc. In the human adult,the dose per person is generally between 1 mg and 1000 mg, by oraladministration, up to several times per day, and between 0.1 mg and 100mg, by parenteral administration, up to several times per day, orcontinuous administration between 1 and 24 hrs. per day intravenously.

As mentioned above, the doses to be used depend on various conditions.Therefore, there are cases in which doses lower than or greater than theranges specified above may be used.

The compounds of the present invention can be administered as solidcompositions, liquid compositions or other compositions for oraladministration, as injections, liniments or suppositories etc. forparenteral administration.

Solid compositions for oral administration include compressed tablets,pills, capsules, dispersible powders and granules. Capsules include hardcapsules and soft capsules.

In such compositions, one or more of the active compound(s) is or areadmixed with at least one inert diluent (such as lactose, mannitol,glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch,polyvinylpyrrolidone, magnesium metasilicate aluminate etc.). Thecompositions also may comprise, as is normal practice, additionalsubstances other than inert diluents: e.g. lubricating agents (such asmagnesium stearate etc.), disintegrating agents (such as cellulosecalcium glycolate etc.), stabilizing agents (such as lactose etc.), andassisting agents for dissolving (such as glutamic acid, asparaginic acidetc.).

The tablets or pills may, if desired, be coated with a film of gastricor enteric material (such as sugar, gelatin, hydroxypropyl cellulose orhydroxypropylmethyl cellulose phthalate etc.), or be coated with morethan two films. Further, the coating may include containment withincapsules of absorbable materials such as gelatin.

Liquid compositions for oral administration includepharmaceutically-acceptable solutions, emulsions, suspensions, syrupsand elixirs. In such compositions, one or more of the active compound(s)is or are contained in inert diluent(s) commonly used in the art(purified water, ethanol etc.). Besides inert diluents, suchcompositions also may comprise adjuvants (such as wetting agents,suspending agents etc.), sweetening agents, flavouring agents, perfumingagents and preserving agents.

Other compositions for oral administration include spray compositionswhich may be prepared by known methods and which comprise one or more ofthe active compound(s). Spray compositions may comprise additionalsubstances other than inert diluents: e.g. stabilizing agents (sodiumsulfate etc.), isotonic buffer (sodium chloride, sodium citrate, citricacid etc.). For preparation of such spray compositions, for example, themethod described in the U.S. Pat. No. 2,868,691 or 3,095,355 (hereinincorporated in their entirety by reference) may be used.

Injections for parenteral administration include sterile aqueous ornon-aqueous solutions, suspensions and emulsions. In such compositions,one more of active compound(s) is or are admixed with at least one inertaqueous diluent(s) (distilled water for injection, physiological saltsolution etc.) or inert non-aqueous diluent(s) (propylene glycol,polyethylene glycol, olive oil, ethanol, POLYSORBATE80 (registered trademark) etc.).

Injections may comprise other inert diluents: e.g. preserving agents,wetting agents, emulsifying agents, dispersing agents, stabilizing agent(lactose etc.), assisting agents, such as assisting agents fordissolving (glutamic acid, asparaginic acid etc.) etc.

They may be sterilized for example, by filtration through abacteria-retaining filter, by incorporation of sterilizing agents in thecompositions or by irradiation. They may also be manufactured in theform of sterile, solid compositions, for example, by freeze-drying,which may be dissolved in sterile water or some other sterile diluent(s)for injection immediately before use.

Other compositions for parenteral administration include liquids forexternal use, and endermic liniments, ointments, suppositories andpessaries which comprise one or more of the active compound(s) and maybe prepared by per se known methods.

BEST MODE TO PRACTICE THE INVENTION

The following reference examples and examples illustrate the presentinvention, but should not be construed to limit the present invention.

The solvents in the parentheses show the developing or eluting solventsand the ratios of the solvents used are by volume in chromatographicseparations, TLC and HPTLC.

NMR in the parentheses show measured solvents. The TLC plate used wasMerck 5715, and the HPTLC plate used was Merck 05642. Silica gel usedwas Merck 7734, except for specifically case.

EXAMPLE 1N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester (1) andN-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester (2)

To a solution ofN-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-bromopentanoicacid.t-butylester [The compound prepared by the method of J. Med. Chem.,37, 563 (1994)] (298 mg) in N,N-dimethylformamide (5 ml) wassuccessively added potassium fluoride (144 mg) and5-(2,6-dichlorophenylmethyl)tetrazole (249 mg). The reaction mixture wasstirred for 1 days at room temperature. The mixture was quenched byaddition of water and extracted with ethyl acetate. The extract waswashed with a saturated aqueous solution of sodium chloride, dried overanhydrous sodium sulfate and concentrated. The residue was purified bycolumn chromatography on NAM-600M silica gel (Nam research institute,registered trade mark) (chloroform:methanol=100:1→50:1) to give thecompounds of example 1 (1) (37 mg) and example 1(2) (147 mg) having thefollowing physical dataly.

EXAMPLE 1 (1)

HPTLC:Rf 0.33 and 0.30 (chloroform: methanol=19:1); NMR (DMSO-d₆): δ8.89 and 8.66 (total 1H, each d, J=7.9 Hz), 8.29 and 8.28 (total 1H,each d, J=7.9 Hz), 7.83 and 7.81 (total 1H, each d, J=7.9 Hz), 7.53 (2H,d, J=9.0 Hz), 7.41 (1H, t, J=9.0 Hz), 7.26-7.11 (5H, m), 5.86, 5.83,5.79 and 5.75 (total 2H, each d, J=18.0 Hz), 4.85 and 4.64 (total 1H,each dt, J=7.9 Hz, 6.7 Hz), 4.35-4.06 (total 4H, m), 2.87-2.72,2.72-2.57 and 2.57-2.35 (total 8H, m), 1.94-1.80 (1H, m), 1.40 and 1.39(total 9H, each s), 1.28 and 1.25 (total 3H, each d, J=9.0 Hz), 0.80,0.76 and 0.71 (total 6H, each d, J=6.7 Hz).

EXAMPLE 1(2)

HPTLC:Rf 0.40 (chloroform: methanol=19:1); NMR (DMSO-d₆): δ 8.80 and8.53 (total 1H, each d, J=7.9 Hz), 8.29 and 8.27 (total 1H, each d,J=7.9 Hz), 7.88 and 7.84 (total 1H, each d, J=7.9 Hz), 7.51 (2H, d,J=9.0 Hz), 7.36 (1H, t, J=9.0 Hz), 7.28-7.12 (5H, m), 5.89, 5.83, 5.79and 5.71 (total 2H, each d, J=18.0 Hz), 4.78 and 4.56 (total 1H, eachdt, J=7.9 Hz, 6.7 Hz), 4.50 and 4.49 (total 1H, each s), 4.22 and 4.21(1H, each dq, J=9.0 Hz, 7.9 Hz), 4.16 and 4.14 (1H, each dd, J=9.0 Hz,7.9 Hz), 2.83-2.70 and 2.70-2.36 (total 8H, m), 1.95-1.80 (1H, m), 1.36and 1.37 (total 9H, each s), 1.24 and 1.22 (total 3H, each d, J=9.0 Hz),0.82 , 0.81 and 0.76 (total 6H, each d, J=6.7 Hz).

EXAMPLE 1(3)-1(6)

By the same procedure as provided in example 1, using correspondingtetrazole compounds instead of 5-(2,6-dichlorophenylmethyl) tetrazole,compounds of the present invention having the following physical datawere obtained.

EXAMPLE 1(3)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(4-methylphenoxy)tetrazol-1-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.21 (chloroform: methanol=19:1); NMR (CDCl₃): δ 7.64-7.54 (1H,m), 7.35-7.12 (10H, m), 6.72-6.61 (1H, m), 6.07-6.00 (1H, m) 5.57 (1H,d, J=18.5 Hz), 5.25 (1H, d, J=18.5 Hz), 4.98-4.81 (1H, m), 4.50-4.30(1H, m), 4.21-4.07 (1H, m), 3.03-2.84, 2.84-2.63 and 2.63-2.52 (total8H, m), 2.34 (3H, s), 2.15-1.95 (1H, m), 1.42 (3H, d, J=8.0 Hz), 1.40(9H, s), 0.87 and 0.82 (each 3H, each d, J=6.8 Hz).

EXAMPLE 1(4)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(4-methylphenoxy)tetrazol-2-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.27 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.79-7.67 (1H,m), 7.31-6.98 (10H, m), 6.40-6.29 (1H, m), 5.69 and 5.68 (total 1H, eachd, J=17.0 Hz), 5.46 and 5.45 (total 1H, each d, J=17.0 Hz), 4.92-4.75(1H, m), 4.59-4.38 (1H, m), 4.32-4.19 (1H, m), 3.01-2.83, 2.83-2.65 and2.65-2.49 (total 8H, m), 2.33 (3H, s), 2.11-1.80 (1H, m), 1.41 (9H, s),1.38 (3H, d, J=8.4 Hz), 0.92-0.73 (6H, m).

EXAMPLE 1(5)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-trifluoromethyltetrazol-2-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.13 (chloroform: methanol=19:1); NMR (DMSO-d₆): δ 9.02-8.92and 8.66-8.55 (total 1H, m), 8.36-8.24 (1H, m), 7.91-7.75 (1H, m),7.30-7.05 (5H, m), 6.17-6.04 (2H, m), 4.91-4.74 and 4.68-4.50 (total 1H,m), 4.32-4.05 (2H, m), 2.90-2.65 and 2.65-2.27 (total 8H, m), 2.00-1.75(1H, m) 1.38 and 1.37 (total 9H, each s), 1.28-1.12 (3H, m), 0.92-0.67(6H, m).

EXAMPLE 1(6)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(N,N-dimethylamino)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.31 (chloroform: methanol=15:1); NMR (DMSO-d₆): δ 8.78 and 8.54(total 1H, each m), 8.29 (1H, m), 7.88 (1H, m), 7.21 (5H, m), 5.61 (2H,m), 4.79 and 4.58 (total 1H, each m), 4.19 (2H, m), 2.94 (6H, s),2.88-2.35 (total 6H, m), 1.90 (1H, m), 1.40 (9H, s), 1.23 (3H, m), 0.80(6H, m).

EXAMPLE 2(1)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

To a solution of compound (1) prepared in example 1 (23 mg) inthioanisole (0.17 ml) and m-cresole (0.15 ml) was added trifluoroaceticacid (2 ml). The reaction mixture was stirred for 30 min at roomtemperature. To the reaction mixture was added toluene, and then themixture was concentrated. The residue was washed with diethyl ether, anddried over to give the compound of the present invention (17 mg) havingthe following physical data.

TLC:Rf 0.31 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.93-8.82 and 8.75-8.64 (total 1H, m), 8.33-8.20 (1H, m), 7.87-7.75 (1H,m), 7.65-7.32 and 7.32-7.05 (total 8H, m), 5.98-5.67 (2H, m), 4.83-4.57(1H, m), 4.41-4.00 (2H, m), 2.95-2.66 and 2.66-2.25 (total 6H, m),2.00-1.74 (1H, m), 1.35-1.15 (3H, m), 0.90-0.62 (6H, m).

EXAMPLE 2(2)-2(6)

By the same procedure as provided in example 2(1), and if necessary, byknown methods converted to accommodate the corresponding salts, usingthe compounds of examples 1(2)-1(6) instead of compound (1) prepared inexample 1, compounds of the present invention having the followingphysical data were obtained.

EXAMPLE 2(2)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.86-8.71 and 8.64-8.52 (total 1H, m), 8.33-8.18 (1H, m), 7.92-7.80 (1H,m), 7.57-7.43 and 7.43-7.30 (3H, m), 7.30-7.07 (5H, m), 6.00-5.75 (2H,m), 4.79-4.63 and 4.63-4.40 (total 1H, m), 4.50 (2H, s), 4.27-4.05 (2H,m), 2.78-2.66 and 2.66-2.25 (total 6H, m), 1.97-1.75 (1H, m), 1.31-1.15(3H, m), 0.88-0.68 (6H, m).

EXAMPLE 2(3)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(4-methylphenoxy)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.34 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.78-8.67 and 8.67-8.54 (1H, m), 8.32-8.16 (1H, m), 7.92-7.80 (1H, m),7.33-7.08 (9H, m), 5.65-5.30 (2H, m), 4.77-4.55 (1H, m), 4.35-4.03 (2H,m), 2.77-2.66 and 2.66-2.37 (total 6H), 2.32 (3H, s), 1.98-1.75 (1H, m),1.30-1.15 (3H, m), 0.87-0.67 (6H, m).

EXAMPLE 2(4)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(4-methylphenoxy)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.51 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.86-8.71 and 8.62-8.52 (1H, m), 8.32-8.18 (1H, m), 7.93-7.79 (1H, m),7.32-7.07 (9H, m), 5.91-5.58 (2H, m), 4.78-4.65 and 4.65-4.49 (1H, m),4.30-4.06 (2H, m), 2.80-2.68 (2H, m), 2.68-2.34 (4H, m), 2.31 (3H, s),2.00-1.75 (1H, m), 1.32-1.15 (3H, m), 0.87-0.70 (6H, m).

EXAMPLE 2(5)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-trifluoromethyltetrazol-2-yl)pentanoicacid

TLC:Rf 0.28 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.98-8.84 and 8.71-8.59 (total 1H, m), 8.35-8.22 (1H, m), 7.92-7.77 (1H,m) 7.32-7.06 (5H, m), 6.26-5.90 (2H, m), 4.81-4.54 (1H, m), 4.35-4.07(2H, m), 2.92-2.30 (6H, m) 2.01-1.85 (1H, m), 1.34-1.15 (3H, m),0.93-0.69 (each 3H, m).

EXAMPLE 2(6)N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-(5-(N,N-dimethylamino)tetrazol-2-yl)pentanoicacid.trifluoroacetic acid salt

TLC:Rf 0.24 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ8.71 and 8.54 (total 1H, each d, J=10 Hz), 8.28 and 8.21 (total 1H, eachd, J=6 Hz), 7.88 and 7.84 (total 1H, each d, J=10 Hz), 7.20 (5H, m),5.70-5.46 (2H, m), 4.70 and 4.55 (total 1H, each m), 4.20 and 4.15(total 2H, each m), 2.93 (6H, s), 2.80-2.40 (total 6H, m), 1.90 (1H, m),1.23 (3H, m), 0.80 (6H, m).

EXAMPLE 3(1)-3(7)

By the same procedure as example 1, using corresponding tetrazolecompound and3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-bromopentanoicacid.t-butylester [The compound was prepared by the method of J. Med.Chem., 37, 563(1994)] instead ofN-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-bromopentanoicacid.t-butylester, compounds of the present invention having thefollowing physical data were obtained.

EXAMPLE 3(1)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 3(3))

HPTLC:Rf 0.24 (benzene:ethyl acetate=1:1); NMR (CDCl₃): δ 7.80 and7.64-7.13 (total 10H, m), 5.82, 5.78, 5.60 and 5.52 (total 2H, each d,J=18.0 Hz), 5.06-4.78 (3H, m), 4.34 and 4.30 (total 2H, each s), 3.56(2H, m), 3.12-2.61 (2H, m), 2.33-1.10 (9H, m), 1.42 and 1.41 (total 9H,each s).

EXAMPLE 3(2)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 3(4))

HPTLC:Rf 0.32 (benzene:ethyl acetate=1:1); NMR (CDCl₃): δ 7.82 and7.68-7.10 (total 10H, m), 5.85-5.50 (2H, m), 5.13-4.75 (3H, m), 4.60 and4.57 (total 2H, each s), 3.51 (2H, m), 3.02-2.50 (2H, m), 2.30-1.20 (9H,m), 1.42 and 1.40 (total 9H, each s).

EXAMPLE 3(3)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 3(1))

HPTLC:Rf 0.29 (benzene:ethyl acetate=1:1); NMR (CDCl₃): δ 7.86-7.08(10H, m), 5.85-5.38 (2H, m), 5.06 (1H, m), 4.96-4.72 (2H, m), 4.60,4.57, 4.33 and 4.28 (total 2H, each s), 3.65-3.30 (2H, m), 3.02-2.50(2H, m), 2.28-1.20 (18H, m).

EXAMPLE 3(4)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 3(2))

HPTLC:Rf 0.42 (benzene:ethyl acetate=1:1); NMR (CDCl₃): δ 7.85-7.10(10H, m), 5.80-5.43 (2H, m), 5.10 (1H, m), 4.82 (2H, m), 4.56 (2H, s),3.60-3.28 (2H, m), 2.87-2.54 (2H, m), 2.29-1.20 (6H, m), 1.46 (3H, d,J=8.0 Hz), 1.33 and 1.32 (total 9H, each s).

EXAMPLE 3(5)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-trifluoromethyltetrazol-2-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 3(6))

HPTLC:Rf 0.39 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.89-7.32 (5H,m), 6.05, 5.95, 5.76 and 5.69 (total 2H, each d, J=17.5 Hz), 5.15-4.75(3H, m), 3.55 (2H, m), 3.08-2.56 (2H, m), 2.32-1.20 (6H, m), 1.48 (3H,d, J=7.5 Hz), 1.42 (9H, s).

EXAMPLE 3(6)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-trifluoromethyltetrazol-2-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 3(5))

HPTLC:Rf 0.27 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.79 and7.62-7.28 (total 5H, m), 6.06, 6.03, 5.84 and 5.76 (total 2H, each d,J=17.5 Hz), 5.01-4.74 (3H, m), 3.55 (2H, m), 3.08-2.56 (2H, m),2.32-1.20 (6H, m), 1.48 (3H, d, J=7.5 Hz), 1.42 (9H, s).

EXAMPLE 3(7)3-(N-(2-(hexahydro-2-oxo-3S-(Phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyletrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.33 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 8.77-8.47 (1H,m), 8.22 (1H, d, J=6.6 Hz), 7.79 (2H, m), 7.46 (3H, m), 7.26 (5H, m),5.65 (2H, m), 5.19-4.62 (3H, m), 4.10 (2H, m), 3.50 (2H, m), 2.80 (1H,m), 2.56 (1H, m), 1.99-1.50 (6H, m), 1.40 (9H, s), 1.36 (3H, m).

EXAMPLE 4(1)-4(7)

By the same procedure as provided in example 2(1), using the compoundsof examples 3(1)-3(7) instead of compound (1) prepared in example 1,compounds of the present invention having the following physical datawere obtained.

EXAMPLE 4(1)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 4(3))

HPTLC:Rf 0.34 and 0.30 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ8.57-8.22 (2H, m), 7.80 (2H, m), 7.60-7.30 (6H, m), 5.89 (2H, m),5.00-4.55 (3H, m), 4.32 (2H, m), 3.51 (2H, m), 2.60 (2H, m), 2.00-1.43(6H, m), 1.31 (3H, m).

EXAMPLE 4(2)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 4(4))

HPTLC:Rf 0.41 and 0.32 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ8.46-8.26 (2H, m), 7.79 (2H, m), 7.60-7.29 (6H, m), 6.06-5.66 (2H, m),4.96-4.54 (3H, m), 4.49 and 4.43 (total 2H, s), 3.50 (2H, m), 2.61-2.36(2H, m), 1.98-1.45 (6H, m), 1.29 (3H, m).

EXAMPLE 4(3)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 4(1))

HPTLC:Rf 0.37 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 8.53-8.26 (2H,m), 7.84 (2H, m), 7.48 (6H, m), 5.86 (2H, m), 5.15 (1H, m), 4.86 (1H,m), 4.66 (1H, m), 4.34 (total 2H, s), 3.5 (2H, m), 2.59 (2H, m),2.02-1.53 (6H, m), 1.33 (3H, m).

EXAMPLE 4(4)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 4(2))

HPTLC:Rf 0.43 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 8.51-8.21 (2H,m), 7.86 (2H, m), 7.60-7.28 (6H, m), 6.00-5.68 (2H, m), 5.11 (1H, m),4.89 (1H, m), 4.68 (1H, m), 4.50 and 4.48 (total 2H, s), 3.50 (2H, m),2.53 (2H, m), 2.00-1.55 (6H, m), 1.33 (3H, m).

EXAMPLE 4(5)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-trifluoromethyltetrazol-2-yl)pentanoic acid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 4(6))

HPTLC:Rf 0.35 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 8.59-8.16 (2H,m), 8.00-7.76 and 7.65-7.40 (total 5H, m), 6.29-6.00 (2H, m), 5.13, 4.89and 4.70 (total 3H, m), 3.6-3.1 (2H, m), 2.66-2.39 (2H, m), 2.00-1.51and 1.48-1.05 (total 9H, m).

EXAMPLE 4(6)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-trifluoromethyltetrazol-2-yl)pentanoic acid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 4(5))

HPTLC:Rf 0.30 and 0.24 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ8.60-8.30 (2H, m), 8.00-7.70 and 7.60-7.30 (total 5H, m), 6.36-5.99 (2H,m), 4.95-4.50 (3H,.m), 3.6-3.1 (2H, m), 2.65-2.40 (2H, m), 1.98-1.20(9H, m).

EXAMPLE 4(7)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoic acid

HPTLC:Rf 0.70 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 8.40(2H, m), 7.85 (2H, m), 7.50 (3H, m), 7.27 (5H, s), 5.72 (2H, m),5.22-4.58 (3H, m), 4.14 (2H, m), 3.45 (4H, m), 2.59 (2H, m) 1.96-1.50(6H, m), 1.31 (3H, m).

REFERENCE EXAMPLE 1 5-(ethoxycarbonylmethyl)tetrazole

The mixture of ethylcyanoacetate (1.53 g), trimethyltinazaide [(CH₃)₃SnN₃] (3.67 g) and toluene (20 ml) was refluxed for 14 h. After thereaction mixture was concentrated under reduced pressure, the residuewas dissolved in ethanol (300 ml). To the thus obtained solution wasadded a 1 N aqueous solution of hydrochloric acid (150 ml), and themixture was stirred for 3 h at room temperature. To the reaction mixturewas added a 1 N aqueous solution of sodium hydroxide until a pH 3 or 4was obtained, and the mixture was concentrated under reduced pressure.To the residue was added water, and the mixture was added chloroform andmethanol, the precipitate solid was filtered, dried to give the titlecompound (783 mg) having the following physical data.

TLC:Rf 0.23 (chloroform:methanol=4:1); NMR (CD₃OD): δ 4.22 (2H, q, J=7.0Hz), 4.12 (2H, s), 1.27 (2H, t, J=7.0 Hz).

REFERENCE EXAMPLE 1(1) 5-styryltetrazole

By the same procedure as provided in reference example 1, using thecompounds of cinnamonitrile instead of ethylcyanoacetate, compoundhaving the following physical data was obtained.

TLC:Rf 0.25 (chloroform:methanol=19:1); NMR (CD₃OD): δ 7.74-7.55 (3H,m), 7.50-7.32 (3H, m), 7.20 (1H, d, J=16.8 Hz).

REFERENCE EXAMPLE 2

5-phenylethyltetrazole

The mixture of the compound prepared in reference example 1(1) (1.0 g),10% palladium on activated carbon (200 mg) and ethanol (40 ml) wasstirred at room temperature for 4 h under an atmosphere of hydrogen gas.The reaction mixture was filtered through Celite (trade mark) and thefiltrate was concentrated to give the title compound having thefollowing physical data.

TLC:Rf 0.25 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 7.38-7.10 (5H,m), 3.26-3.12 (2H, m), 3.11-2.97 (2H, m).

REFERENCE EXAMPLE 3 1-(4-methoxyphenylmethyl)tetrazole

The mixture of 4-methoxybenzylamine (27 g), trimethylorthoformate (52.4ml), sodium azide (19.2 g) and acetic acid (176 ml) was stirred at 80°C. for 14 h. The reaction mixture was concentrated under reducedpressure, the residue was dissolved in water and extracted with ethylacetate. The extract was washed with a 1 N aqueous solution ofhydrochloric acid, water, a saturated aqueous solution of sodiumhydrocarbonate and a saturated aqueous solution of sodium chloride,successively, dried over anhydrous sodium sulfate and concentrated. Theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=1:1) to give the title compound (17.6 g) havingthe following physical data.

TLC:Rf 0.34 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.46 (1H, s),7.26 (2H, d, J=8.5 Hz), 6.92 (2H, d, J=8.5 Hz), 5.52 (2H, s), 3.81 (3H,s).

REFERENCE EXAMPLE 4 1-(4-methoxyphenylmethyl)-5-bromotetrazole

To a solution of the compound prepared in reference example 3 (5.0 g) intetrahydrofuran (112 ml) and N,N,N′,N′-tetramethylethylenediamine (11ml) was added 1.67 M of n-butyllithium in hexane solution (15.8 ml) at−68° C. under an atmosphere of argon. After the mixture was stirred for10 min, to the mixture was added dropwise the solution of bromine (1.36ml) in tetrahydrofuran (8 ml) at same temperature. The mixture wasstirred for 30 min at −78° C., and the mixture was warmed up at 0° C.The mixture was concentrated under reduced pressure, the residue wasdissolved in water and extracted with ethyl acetate. The extract waswashed with a saturated aqueous solution of sodium chloride, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedby column chromatography on silica gel (hexane:ethyl acetate=2:1) togive the title compound (2.28 g) having the following physical data.

TLC:Rf 0.63 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.29 (2H, d,J=8.5 Hz), 6.87 (2H, d, J=8.5Hz), 5.48 (2H, s), 3.80 (3H, s).

REFERENCE EXAMPLE 5 1-(4-methoxyphenylmethyl)-5-methoxytetrazole

To a solution of the compound prepared in reference example 4 (507 mg)in methanol (5 ml) was added sodium methoxide (509 mg) at 0° C. Themixture was stirred for 4 h at 0° C. The mixture was concentrated underreduced pressure, the residue was dissolved in ice and a 1 N aqueoussolution of hydrochloric acid and extracted with ethyl acetate. Theextract was washed with water and a saturated aqueous solution of sodiumchloride, dried over anhydrous magnesium sulfate and concentrated. Theresidue was purified by column chromatography on NAM-600M silica gel(Nam research institute, registered trade mark) (hexane:ethylacetate=2:1) to give the title compound (335 mg) having the followingphysical data.

TLC:Rf 0.53 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.24 (2H, d,J=8.5 Hz), 6.87 (2H, d, J=8.5 Hz), 5.18 (2H, s), 4.22 (3H, s), 3.79 (3H,s).

REFERENCE EXAMPLE 6 5-methoxytetrazole

To a solution of the compound prepared in reference example 5 (335 mg)in acetonitrile (8 ml) was added ammonium cerium nitrate [CAN] (4.41 g)in water (6 ml) at 0° C. The mixture was stirred for 1 h at roomtemperature. The reaction mixture was poured into a saturated aqueoussolution of sodium chloride and extracted with ethyl acetate. Theextract was washed with a saturated aqueous solution of sodium chloride,dried over anhydrous sodium sulfate and concentrated. The residue waswashed with diethylether to give the title compound (66 mg) having thefollowing physical data.

TLC:Rf 0.20 (chloroform:methanol=4:1); NMR (CD₃OD): δ 4.15 (3H, s).

REFERENCE EXAMPLE 7 5-phenylmethyltetrazole

The mixture of 5-(2,6-dichlorophenylmethyl)tetrazole (355 mg), 5%palladium on activated carbon (93 mg) and methanol (8 ml) was stirredfor 1 h room temperature under an atmosphere of hydrogen gas. Thereaction mixture was filtered through Celite (trade mark) and thefiltrate was concentrated to give the title compound having thefollowing physical data.

TLC:Rf 0.50 (chloroform:methanol:acetic acid=18:1:1).

EXAMPLE 5(1)-5(160)

By the same procedure as example 1, usingN-benzyloxycarbonyl-3-amino-4-oxo-5-bromopentanoic acid.t-butylester[see EP 0623592, Example 1] instead ofN-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-bromopentanoicacid.t-butylester and the corresponding tetrazole compounds (for examplethe compounds prepared in reference example 1, reference example 1(1),reference example 2, reference example 6 or reference example 7), thecompounds of the present invention having the following physical datawere obtained.

EXAMPLE 5(1)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.45 (hexane:ethyl acetate=3:2);

NMR (CDCl₃): δ 7.44-7.15 (8H, m), 5.86 (1H, d, J=8.0 Hz), 5.69 (1H, d,J=8.7 Hz), 5.55 (1H, d, J=18.7 Hz), 5.20 (2H, s), 4.70-4.54 (1H, m),4.33 (1H, d, J=16.4 Hz), 4.23 (1H, d, J=16.4 Hz), 3.10 (1H, dd, J=17.6,4.4 Hz), 2.76 (1H, dd, J=17.6, 5.0 Hz), 1.41 (9H, s).

EXAMPLE 5(2)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.66 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.40-7.10 (8H,m), 5.92 (1H, d, J=8.4 Hz), 5.76 (1H, d, J=17.7 Hz), 5.58 (1H, d, J=17.7Hz), 5.16 (2H, s), 4.70-4.55 (3H, m), 2.99 (1H, dd, J=17.5, 5.0 Hz),2.69 (1H, dd, J=17.5, 4.8 Hz), 1.41 (9H, s).

EXAMPLE 5(3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.14 (hexane:ethyl acelate=2:1); NMR (CDCl₃): δ 7.41-7.14 (10H,m), 5.87-5.73 (1H, m), 5.32 (2H, s), 5.15 (2H, s), 4.60-4.44 (1H, m),4.25 and 4.04 (each 1H, d, J=17.0 Hz), 3.03 and 2.71 (each 1H, dd,J=17.0 Hz, 5.0 Hz), 1.43 (9H, s).

EXAMPLE 5(4)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-phenylmethyltetrazol-2-yl)pentanoic acid.t-butylester

TLC;Rf 0.36 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.42-7.16 (10H,m), 6.05-5.90 (1H, m), 5.78 and 5.60 (each 1H, d, J=18.0 Hz), 5.16 (2H,s), 4.73-4.56 (1H, m), 4.26 (2H, s), 2.98 (1H, dd, J=17.4 Hz, 4.4 Hz),2.70 (1H, dd, J=17.4 Hz, 5.0 Hz), 1.41 (9H, s).

EXAMPLE 5(5)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methylphenoxy)tetrazol-1-yl)pentanoicacid.t-butylester

NMR (CDCl₃): δ 7.39 (5H, brs), 7.21 (4H, brs), 5.97 (1H, d, J=8.9 Hz),5.53 (1H, d, J=18.3 Hz), 5.32 (1H, d, J=18.3 Hz), 5.20 (2H, s),4.78-4.56 (1H, m), 3.07 (1H, dd, J=17.5, 4.2 Hz), 2.72 (1H, dd, J=17.5,4.9 Hz), 2.36 (3H, s), 1.39 (9H, s).

EXAMPLE 5(6)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methylphenoxy)tetrazol-2-yl)pentanoicacid.t-butylester

NMR (CDCl₃): δ 7.38 (5H, brs), 7.18 (4H, brs), 5.95 (1H, d, J=9.0 Hz),5.71 (1H, d, J=17.4 Hz), 5.54 (1H, d, J=17.4 Hz), 5.18 (2H, s),4.76-4.58 (1H, m), 3.02 (1H, dd, J=17.6, 4.8 Hz), 2.70 (1H, dd, J=17.6,4.8 Hz), 2.35 (3H, s), 1.42 (9H, s).

EXAMPLE 5(7)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-t-butylphenoxy)tetrazol-1-yl)pentanoicacid.t-butylester

NMR (CDCl₃): δ 7.42-7.08 (9H, m), 5.97 (1H, d, J=8.8 Hz), 5.54 (1H, d,J=18.0 Hz), 5.33 (1H, d, J=18.0 Hz), 5.19 (2H, s), 4.74-4.60 (1H, m),3.08 (1H, dd, J=18.0, 4.0 Hz), 2.72 (1H, dd, J=18.0, 4.0 Hz), 1.37 (9H,s), 1.31 (9H, s).

EXAMPLE 5(8)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-t-butylphenoxy)tetrazol-2-yl)pentanoicacid.t-butylester

NMR (CDCl₃): δ 7.42-7.20 (8H, m), 7.06 (1H, 8 J=8.0 Hz), 5.95 (1H, d,J=9.4 Hz), 5.71 (1H, d, J=17.7 Hz), 5.55 (1H, d, J=17.7 Hz), 5.17 (2H,s), 4.73-4.55 (1H, m), 3.02 (1H, dd, J=17.5, 4.6 Hz), 2.71 (1H, dd,J=17.5, 4.9 Hz), 1.41 (9H, s), 1.31 (9H, s).

EXAMPLE 5(9)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-styryltetrazol-1-yl)pentanoicacid.t-butylester

NMR (CDCl₃): δ 7.93 (1H, δ J=15.9 Hz), 7.59 (2H, brs), 7.54-7.18, (8H,m), 6.80 (1H, d, J=15.9 Hz), 5.80 (1H, d, J=8.6 Hz), 5.63 (2H, brs),5.20 (2H, s), 4.66 (1H, brs), 3.24-3.00 (1H, m), 2.93-2.79 (1H, m), 1.41(9H, s).

EXAMPLE 5(10)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-styryltetrazol-2-yl)pentanoicacid.t-butylester

NMR (CDCl₃): δ 7.76 (1H, δ J=16.5 Hz), 7.68-7.31 (10H, m), 7.16 (1H, d,J=16.5 Hz) 5.98 (1H, d, J=9.6 Hz), 5.84(1H, d, J=17.9 Hz), 5.67 (1H, d,J=17.9 Hz), 5.19 (2H, s), 4.80-4.62 (1H, m), 3.04 (1H, dd, J=17.4, 4.4Hz), 2.74 (1H, dd, J=17.4, 4.9 Hz), 1.44 (9H, s).

EXAMPLE 5(11)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-phenylethyltetrazol-1-yl)pentanoic acid.t-butylester

NMR (CDCl₃): δ 7.64-7.05 (10H, m), 5.72 (1H, d, J=9.1 Hz), 5.21 (1H, d,J=18.7 Hz), 5.18 (2H, s), 5.08 (1H, d, J=18.7 Hz), 4.65-4.45 (1H, m),3.20-2.85 (5H, m), 2.71 (1H, dd, J=17.7, 5.0 Hz), 1.38 (9H, s).

EXAMPLE 5(12)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-phenylethyltetrazol-1-yl)pentanoic acid.t-butylester

NMR (CDCl₃): δ 7.65-7.10 (10H, m), 5.94 (1H, d, J=9.1 Hz), 5.79 (1H, d,J=17.8 Hz), 5.62 (1H, d, J=17.8 Hz), 5.19 (2H, s), 4.77-4.57 (1H, m),3.30 3.06 (4H, m), 3.01 (1H, dd, J=17.5, 4.5 Hz), 2.72 (1H, dd, J=17.5,4.8 Hz), 1.43 (9H, s).

EXAMPLE 5(13)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-methoxytetrazol-1-yl) pentanoicacid.t-butylester

HPTLC:Rf 0.10 (hexane:ethyl acelate=2:1); NMR (CDCl₃): δ 7.38 (5H, m),5.95 (1H, brs), 5.35 and 5.13 (each 1H, each d, J=138.0 Hz), 5.18 (2H,s), 4.62 (1H, m), 4.18 (3H, s), 3.03 (1H, dd, J=17.0, 4.5 Hz), 2.70 (1H,dd, J=17.0, 5.0 Hz), 1.42 (9H, s).

EXAMPLE 5(14)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-methoxytetrazol-2-yl) pentanoicacid.t-butylester

HPTLC:Rf 0.33 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.38 (5H, m),5.93 (1H, brs), 5.67 and 5.50 (each 1H, each d, J=18.5 Hz), 5.16 (2H,s), 4.65 (1H, m), 4.09 (3H, s), 3.02 (1H, dd, J=17.0, 4.5 Hz), 2.71 (1H,dd, J=17.0, 5.0 Hz), 1.42 (9H, s).

EXAMPLE 5(15) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(N,N-dibenzylamino)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.65 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.23-7.15 (15H,m), 5.93 (1H, d, J=10.0 Hz), 5.61 and 5.45 (each 1H, d, J=17.5 Hz), 5.16(2H, s), 4.72-4.50 (1H, m), 4.61 (4H, s), 2.99 and 2.70 (each 1H, dd,J=17.5 Hz, 5.0 Hz), 1.42 (9H, s).

EXAMPLE 5(16)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-trifluoromethyltetrazol-1-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.39 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.39 (5H, m),6.04-5.60 (3H, m), 5.20 (2H, s), 4.67 (1H, m), 3.09 (1H, dd, J=18.0, 4.5Hz), 2.73 (1H, dd, J=18.0, 5.0 Hz), 1.42 (9H, s).

EXAMPLE 5(17)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-trifluoromethyltetrazol-2-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.43 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.39 (5H, m),6.04-5.68 (3H, m), 5.19 (2H, s), 4.69 (1H, m), 3.07 (1H, dd, J=18.0, 4.5Hz), 2.73 (1H, dd, J=18.0, 5.0 Hz), 1.43 (9H, s).

EXAMPLE 5(18)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(ethoxycarbonylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.36 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.44-7.32 (5H,m), 5.94 (1H, d, J=8.0 Hz), 5.82 and 5.68 (each 1H, both d, J=18.0 Hz),5.18 (2H, s), 4.66 (1H, m), 4.20 (2H, q, J=7.0 Hz), 4.00 (2H, s), 3.00(1H, dd, J=18.0, 4.0 Hz), 2.73 (1H, dd, J=18.0, 5.0 Hz), 1.42 (9H, s),1.27 (3H, t, J=7.0 Hz).

EXAMPLE 5(19)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylthiotetrazol-1-yl) pentanoicacid.t-butylester

TLC:Rf 0.38 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.39 (5H, m),5.95 (1H, m), 5.50 (1H, d, J=16 Hz), 5.30 (1H, d, J=16 Hz), 5.20 (2H,s), 4.63 (1H, m), 3.30 (2H, q, J=7 Hz), 3.05 (1, dd, J=17.5, 5 Hz), 2.70(1H, dd, J=17.5, 5 Hz), 1.42 (12H, m).

EXAMPLE 5(20)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylthiotetrazol-2-yl) pentanoicacid.t-butylester

TLC:Rf 0.54 (hexane:ethyl acetate=3:2);

NMR (CDCl₃): δ 7.39 (5H, m), 5.95 (1H, m), 5.80 (1H, d, J=16 Hz), 5.60(1H, d, J=16 Hz), 5.16 (2H, s), 4.63 (1H, m), 3.20 (2H, q, J=7 Hz),3.01(1H, dd, J=17.5, 5 Hz), 2.70 (1H, dd, J=17.5, 5 Hz), 1.41 (12H, m).

EXAMPLE 5(21)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(ethoxycarbonylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.26 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.44-7.30 (5H,m), 5.89-5.58 (3H, m), 5.17 (2H, s), 4.62 (1H, m), 4.18 (2H, q, J=7.0Hz), 4.03 and 3.82 (each 1H, each d, J=17.0 Hz), 3.09 and 2.77 (each 1H,each dd, J=17.0, 5.0 Hz), 1.42 (9H, s), 1.27 (3H, t, J=7.0 Hz).

EXAMPLE 5(22) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-((4-chlorophenyl)thiomethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.62 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.38 (5H, m),7.30 and 7.22 (total 4H, each d, J=9.0 Hz), 5.94 (1H, d, J=10.0 Hz),5.79 (1H, d, J=17.5 Hz), 5.60 (1H, d, J=17.5 Hz), 5.18 (2H, s), 4.64(1H, m), 4.28 (2H, s), 3.00 (1H, dd, J=17.5 Hz and 5.0 Hz), 2.70 (1H,dd, J=17.5 Hz and 5.0 Hz), 1.40 (9H, s).

EXAMPLE 5(23) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-((4-chlorophenyl)thiomethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.46 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.38 (5H, m),7.22 (4H, m), 5.80 (1H, d, J=10.0 Hz), 5.75 (1H, d, J=7.5 Hz), 5.60 (1H,d, J=17.5 Hz), 5.20 (2H, s), 4.64 (1H, m 4.28 and 4.08 (total 2H, eachd, J=15.0 Hz), 3.10 (1H, dd, J=17.5 Hz and 5.0 Hz), 2.78 (1H, dd, J=17.5Hz and 5.0 Hz), 1.40 (9H, s).

EXAMPLE 5(24)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-phenylpropyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.36 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.98 (1H, d,J=9.5 Hz), 7.42-7.10 (10H, m), 5.91 (2H, s), 5.10 (2H, s), 4.75-4.57(1H, m) 2.92-2.55 (6H, m), 2.10-1.90 (2H, m), 1.38 (9H, s).

EXAMPLE 5(25)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-phenylpropyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.14 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.07 (1H, d,J=9.5 Hz), 7.42-7.08 (10H, m), 5.71 (2H, s), 5.11 (2H, s), 4.72-4.57(1H, m), 2.87-2.54 (6H, m), 2.05-1.84 (2H, m), 1.38 (9H, s).

EXAMPLE 5(26)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenyloxy)tetrazol-2-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.44-7.12 (8H,m), 5.92 (1H, m), 5.70 and 5.53 (each 1H, each d, J=17.5 Hz), 5.16 (2H,s), 4.63 (1H, m), 3.01 and 2.69 (each 1H, each dd, J=17.0, 5.0 Hz), 1.41(9H, s).

EXAMPLE 5(27)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenyloxy)tetrazol-1-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.44 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.47-7.14 (8H,m), 6.00 (1H, m), 5.69-5.26 (2H, m), 5.19 (2H, brs), 4.69 (1H, br), 3.08and 2.73 (each 1H, each m), 1.40 (9H, s).

EXAMPLE 5(28)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chlorophenyloxymethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.62 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.38 (6H, m),7.20 (1H, d, J=6.0 Hz), 7.10 (1H, d, J=6.0 Hz), 6.94 (1H, m), 5.95 (1H,d, J=10.0 Hz), 5.88 (1H, d, J=17.5 Hz), 5.70 (1H, d, J=17.5 Hz), 5.42(2H, s), 5.18 (2H, s), 4.65 (1H, m), 3.01 (1H, dd, J=17.5 Hz and 5.0Hz), 2.70 (1H, dd, J=17.5 Hz and 5.0 Hz), 1.42 (9H, s).

EXAMPLE 5(29)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chlorophenyloxymethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.48 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.38 (6H, m),7.20 (1H, d, J=6.0 Hz), 6.98 (2H, m), 6.08 (1H, d, J=19.0 Hz), 5.88 (1H,d, J=10.0 Hz), 5.75 (1H, d, J=19.0 Hz), 5.50 and 5.30 (total 2H, each d,J=12.5 Hz), 5.18 (2H, s), 4.68 (1H, m), 3.01 (1H, dd, J=17.5 Hz and 5.0Hz), 2.68 (1H, dd, J=17.5 Hz and 5.0 Hz), 1.25 (9H, s).

EXAMPLE 5(30)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methoxycarbonylethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.50 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.45-7.30 (5H,m), 5.94 (1H, d, J=10.0 Hz), 5.76 (1H, d, J=17.0 Hz), 5.61 (1H, d,J=17.0 Hz), 5.18 (2H, s), 4.75-4.50 (1H, m), 3.70 (3H, s), 3.23 (2H, t,J=6.5 Hz), 3.00 (1H, dd, J=16.0 and 4.5 Hz), 2.86 (2H, t, J=6.5 Hz),2.70 (1H, dd, J=16.0 and 5.0 Hz), 1.42 (9H, s).

EXAMPLE 5(31)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methoxycarbonylethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.25 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.43-7.29 (5H,m), 5.96 (1H, d, J=9.0 Hz), 5.68 (1H, d, J=19.5 Hz), 5.55 (1H, d, J=19.5Hz), 5.19 (2H, s), 4.72-4.51 (1H, m), 3.65 (3H, s), 3.06 (1H, dd, J=16.5and 5.0 Hz), 2.92 (4H, brs), 2.73 (1H, dd, J=16.5 and 5.5 Hz), 1.42 (9H,s).

EXAMPLE 5(32)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrrol-2-ylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.65 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.46-7.28 (5H,m), 6.51 (1H, m), 5.98 (1H, m), 5.87 (1H, d, J=9.0 Hz), 5.73 (1H, d,J=17.8 Hz), 5.55 (1H, d, J=17.8 Hz), 5.11 (2H, s), 4.75-4.54 (1H, m),4.18 (2H, s), 3.51 (3H, s), 2.94 (1H, dd, J=17.2 and 4.4 Hz), 2.64 (1H,dd, J=17.2 Hz and 4.8 Hz), 1.36 (9H, s).

EXAMPLE 5(33)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrrol-2-ylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.51 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.48-7.30 (5H,m), 6.56 (1H, m), 6.18-5.92 (2H, m), 5.83 (1H, d, J=9.1 Hz), 5.44 (1H,d, J=18.4 Hz), 5.30 (1H, d, J=18.4 Hz), 5.18 (2H, s), 4.64-4.45 (1H, m),4.31 (1H, d, J=16.8iHz), 4.12 (1H, d, J=16.8 Hz), 3.44 (3H, s), 2.97(1H, dd, J=17.5 and 4.6 Hz), 2.66 (1H, dd, J=17.5 and 4.8 Hz), 1.43 (9H,s).

EXAMPLE 5(34)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-2-ylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.16 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.60-8.46 (1H,m), 7.71-7.54 (1H, m), 7.52-7.07 (7H, m), 5.99 (1H, d, J=8.8 Hz), 5.80(1H, d, J=17.8 Hz), 5.65 (1H, dd, J=17.8 Hz), 5.16 (2H, s), 4.75-4.50(1H, m), 4.48 (2H, s), 3.00 (1H, dd, J=17.6 and 4.8 Hz), 2.72 (1H, dd,17.6 and 5.0 Hz), 1.41 (9H, s).

EXAMPLE 5(35)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-2-ylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.07 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.50-8.36 (1H,m), 7.71-7.56 (1H, m), 7.52-7.07 (7H, m), 6.00 (1H, d, J=8.2 Hz), 5.93(1H, d, J=18.4 Hz), 5.70 (1H, d, J=18.4 Hz), 5.17 (2H, s), 4.77-4.54(1H, m), 4.33 (2H, s), 3.03 (1H, dd, J=22.1 and 4.6 Hz), 2.74 (1H, dd,J=22.1 and 5.0 Hz), 1.39 (9H, s).

EXAMPLE 5(36)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-3-ylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.61 (chloroform:methanol:acetic acid=18:1:1); NMR (CDCl₃): δ8.80-8.30 (2H, m), 7.70-7.60 (1H, m), 7.50-7.21 (1H, m), 5.98 (1H, d,J=9.2 Hz), 5.80 (1H, d, J=17.7 Hz), 5.63 (1H, d, J=17.7 Hz), 5.17 (2H,s), 4.75-4.56 (1H, m), 4.27 (2H, s), 3.01 (1H, dd, J=17.4, 4.6 Hz), 2.71(1H, dd, J=17.4, 4.9 Hz), 1.42 (9H, s).

EXAMPLE 5(37)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-3-ylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.50 (chloroform:methanol:acetic acid=18:1:1); NMR (CDCl₃): δ8.75-8.35 (2H, m), 7.65-7.56 (1H, m), 7.50-7.04 (1H, m), 5.80 (1H, d,J=8.5 Hz), 5.47 (2H, s), 5.18 (2H, s), 4.66-4.52 (1H, m), 4.20 (1H, d,J=16.4H), 4.02 (1H, d, J=16.4 Hz), 3.09 (1H, dd, J=17.6, 4.5 Hz), 2.77(1H, dd, J=17.6, 5.2 Hz), 1.43 (9H, s).

EXAMPLE 5(38)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-difluorophenylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.45 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.70-7.15 (6H,m), 7.03-6.70 (2H, m), 5.92 (1H, d, J=9.2 Hz), 5.76 (i1H, d, J=17.9 Hz),5.58 (1H, d, J=17.9 Hz), 5.16 (2H, s), 4.73-4.52 (1H, m), 4.31 (2H, s),2.99 (1H, dd, J=17.3, 4.6 Hz), 2.69 (1H, dd, J=17.3, 4.9 Hz), 1.41 (9H,s).

EXAMPLE 5(39)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-difluorophenylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.25 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.60-7.10 (6H,m), 7.00-6.85 (2H, m), 5.88 (1H, d, J=8.4 Hz), 5.66 (1H, d, J=18.7 Hz),5.49 (1H, d, J=18.7 Hz), 5.19 (2H, s), 4.74-4.53 (1H, m), 4.07 (2H, s),3.07 (1H, dd, J=17.5, 4.6 Hz), 2.75 (1H, dd, J=17.5, 4.9 Hz), 1.41 (9H,s).

EXAMPLE 5(40)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(phenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.26 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.62-7.49 and7.43-7.29 (total 10H, m), 5.93 (1H, d, J=8.5 Hz), 5.79 and 5.62 (each1H, each d, J=17.5 Hz), 5.16 (2H, s), 4.63 (1H, m), 3.00 and 2.70 (each1H, each dd, J=17.5, 5.0 Hz), 1.40 (9H, s).

EXAMPLE 5(41)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(phenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.19 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.58-7.28 (10H,m), 5.94 (1H, d, J=8.0 Hz), 5.58 and 5.42 (each 1H, each d, J=17.5 Hz),5.19 (2H, s), 4.60 (1H, m), 3.04 and 2.70 (each 1H, each dd, J=17.5, 5.0Hz), 1.41 (9H, s).

EXAMPLE 5(42)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.42 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.50-7.23 (8H,m), 5.93 (1H, d, J=8.0 Hz), 5.77 and 5.58 (each 1H, each d, J=17.5 Hz),5.16 (2H, s), 4.62 (1H, m), 3.00 and 2.69 (each 1H, each dd, J=17.5, 5.0Hz), 1.39 (9H, s).

EXAMPLE 5(43)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.30 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.50-7.25 (8H,m), 5.98 (1H, d, J=8.0 Hz), 5.69 and 5.52 (each 1H, each d, J=17.5 Hz),5.21 (2H, s), 4.68 (1H, m), 3.10 and 2.75 (each 1H, each dd, J=17.5, 5.0Hz), 1.43 (9H, s).

EXAMPLE 5(44)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethylphenylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.71 (hexane:ethyl:acetate=3:2); NMR (CDCl₃): δ 7.46-7.20 (5H,m), 7.13-6.92 (2H, m), 5.93 (1H, d, J=8.6 Hz), 5.73 (1H, d, J=18.0 Hz),5.55 (1H, d, J=18.0 Hz), 5.15 (2H, s), 4.72-4.64 (1H, m), 4.25 (2H, s),2.98 (1H, dd, J=17.3, 4.4 Hz), 2.67 (1H, dd, J=17.3, 4.8 Hz), 2.38 (6H,s), 1.41 (9H, s).

EXAMPLE 5(45)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethylphenylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.40 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.50-7.25 (5H,m), 7.18-6.95 (2H, m), 5.80 (1H, d, J=8.6 Hz), 5.45 (1H, d, J=18.6 Hz),5.31 (1H, d, J=18.6 Hz), 5.17 (2H, s), 4.51-4.35 (1H, m), 4.05 (2H, s),2.98 (1H, dd, J=17.7, 4.6 Hz), 2.69 (1H, dd, J=17.7, 4.9 Hz), 2.18 (6H,s), 1.40 (9H, s).

EXAMPLE 5(46)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(cyclohexylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.72 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.42-7.30 (5H,m), 5.95 (1H, d, J=9.0 Hz), 5.78 (1H, d, J=17.8 Hz), 5.61 (1H, d, J=17.8Hz), 5.17 (2H, s), 4.72-4.50 (1H, m), 3.00 (1H, dd, J=17.4, 4.4 Hz),2.84-2.62 (3H, m), 2.00-1.50 (6H, m), 1.42 (9H, s), 1.36-0.85 (5H, m).

EXAMPLE 5(47)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(cyclohexylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.46 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.45-7.30 (5H,m), 5.85 (1H, d, J=8.8 Hz), 5.49 (2H, s), 5.19 (2H, s), 4.68-4.54 (1H,m), 3.09 (1H, dd, J=17.4, 4.4 Hz), 2.75 (1H, dd, J=17.4, 5.2 Hz), 2.54(2H, d, J=7.2 Hz), 2.00-1.51 (6H, m), 1.43 (9H, s), 1.37-0.80 (5H, m).

EXAMPLE 5(48)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methylphenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.65 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.48 (2H, d,J=8.0 Hz), 7.42-7.30 (5H, m), 7.17 (2H, d, J=8.0 Hz), 5.93 (1H, d, J=9.0Hz), 5.77 (1H, d, J=17.8 Hz), 5.59 (1H, d, J=17.8 Hz), 5.16 (2H, s),4.71-4.56 (1H, m), 3.00 (1H, dd, J=17.4, 4.4 Hz), 2.69 (1H, dd, J=17.4,4.9 Hz), 2.35 (3H, s), 1.41 (9H, s).

EXAMPLE 5(49)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methylphenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.52 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.53-7.28 (7H,m), 7.18 (2H, d, J=8.0 Hz), 5.95 (1H, d, J=8.7 Hz), 5.57 (1H, d, J=18.4Hz), 5.40 (1H, d, J=18.4 Hz), 5.19 (2H, s), 4.73-4.52 (1H, m), 3.04 (1H,dd, J=17.7, 4.6 Hz), 2.70 (1H, dd, J=17.7, 4.9 Hz), 2.35 (6H, s), 1.43(9H, s).

EXAMPLE 5(50)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.63 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.50 (2H, d,J=8.6 Hz), 7.42-7.30 (5H, m), 7.33 (2H, d, J=8.6 Hz), 5.93 (1H, d, J=8.8Hz), 5.80 (1H, d, J=17.6 Hz), 5.62 (1H, d, J=17.6 Hz), 5.17 (2H, s),4.72-4.56 (1H, m), 3.02 (1H, dd, J=17.4, 4.4 Hz), 2.70 (1H, dd, J=17.4,4.7 Hz), 1.41 (9H, s).

EXAMPLE 5(51)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.51 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.48 (2H, d,J=8.6 Hz), 7.43-7.28 (7H, m), 5.94 (1H, d, J=9.0 Hz), 5.60 (1H, d,J=18.3 Hz), 5.44 (1H, d, J=18.3 Hz), 5.20 (2H, s), 4.70-4.54 (1H, m),3.06 (1H, dd, J=17.6, 4.2 Hz), 2.71 (1H, dd, J=17.6, 4.7 Hz), 1.43 (9H,s).

EXAMPLE 5(52)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-4-yl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.55 (ethyl acetate); NMR (CDCl₃): δ 8.58-8.48 (2H, m), 7.38 (5H,m), 7.27-7.18 (2H, m), 5.95 (1H, d, J=8.4 Hz), 5.83 (1H, d, J=17.6 Hz),5.65 (1H, d, J=17.6 Hz), 5.18 (2H, s), 4.77-4.50 (1H, m), 4.27 (2H, s),3.04 (1H, dd, J=17.4 and 4.6 Hz), 2.71 (1H, dd, J=17.4 and 4.8 Hz), 1.42(9H, s).

EXAMPLE 5(53)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-4-yl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.37 (ethyl acetate); NMR (CDCl₃): δ 8.64-8.50 (2H, m), 7.38 (5H,brs), 7.25-7.11 (2H, m), 5.75-5.65 (1H, m), 5.58-5.31 (2H, m), 5.17 (2H,s), 4.69-4.45 (1H, m), 4.20 (1H, d, J=16.6 Hz), 4.01 (1H, d, J=16.6 Hz),3.19-2.67 (2H, m), 1.43 (9H, s).

EXAMPLE 5(54)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3,5-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.59 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.45-7.28 (8H,m), 5.94 (1H, d, J=8.5 Hz), 5.84 and 5.68 (each 1H, each d, J=17.5 Hz),5.17 (2H, s), 4.66 (1H, m), 3.03 and 2.71 (each 1H, each dd, J=17.5, 5.0Hz), 1.40 (9H, s).

EXAMPLE 5(55)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3,5-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

HPTLC:Rf 0.46 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.46-7.30 (8H,m), 5.92 (1H, d, J=8.5 Hz), 5.64 and 5.48 (each 1H, each d, J=17.5 Hz),5.19 (2H, s), 4.63 (1H, m), 3.07 and 2.73 (each 1H, each dd, J=17.5, 5.0Hz), 1.42 (9H, s).

EXAMPLE 5(56)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrimidin-2,4-dion-3-ylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.38 (chloroform:methanol=20:1); NMR (CDCl₃): δ 7.38 (5H, m),7.15 (1H, d, J=8 Hz), 6.00 (1H, d, J=10 Hz), 5.79 (1H, d, J=8 Hz), 5.72(1H, d, J=17 Hz), 5.62 (1H, d, J=17 Hz), 5.43 (2H, s), 5.18 (2H, s),4.61 (1H, m), 3.40 (3H, s), 2.93 (1H, dd, J=18 and 5 Hz), 2.71 (1H, dd,J=15 and 5 Hz), 1.40 (9H, s).

EXAMPLE 5(57)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrimidin-2,4-dion-3-ylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.32 (chloroform:methanol=20:1); NMR (CDCl₃): δ 7.40 (5H, m),7.13 (1H, d, J=8 Hz), 5.93 (1H, d, J=10 Hz), 5.92 (1H, d, J=17 Hz), 5.75(1H, d, J=17 Hz), 5.72 (1H, d, J=8 Hz), 5.30 (1H, d, J=16 Hz), 5.20 (2H,s), 5.09 (1H, d, J=16 Hz), 4.68 (1H, m), 3.39 (3H, s), 3.03 (1H, dd,J=17 and 5 Hz), 2.78 (1H, dd, J=17 and 5 Hz), 1.40 (9H, s).

EXAMPLE 5(58)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloroethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.68 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.39 (5H, m),5.94 (1H, d, J=8.8 Hz), 5.82 (1H, d, J=17.8 Hz), 5.65 (1H, d, J=17.8Hz), 5.18 (2H, s), 4.72-4.60 (1H, m), 3.92 (2H, t, J=7.0 Hz), 3.39 (2H,t, J=7.0 Hz), 3.02 (1H, dd, J=17.4 and 4.2 Hz), 2.72 (1H, dd, J=17.4 and4.8 Hz), 1.43 (9H, s).

EXAMPLE 5(59)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloroethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.46 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.39 (5H, m),5.79 (1H, d, J=8.2 Hz), 5.74-5.49 (2H, m), 5.20 (2H, s), 4.70-4.52 (1H,m), 3.92 (2H, t, J=7.0 Hz), 3.24-3.02 (3H, m), 2.77 (1H, dd, J=17.4 and5.2 Hz), 1.44 (9H, s).

EXAMPLE 5(60)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(phenylcarbonyl)tetrazol-2-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.35 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.36 (2H, d,J=7.0 Hz), 7.73-7.29 (3H, m), 7.37 (5H, m), 6.11-5.74 (3H, m), 5.18 (2H,s), 4.73 (1H, m), 3.05 and 2.77 (each 1H, each dd, J=17.0, 5.0 Hz), 1.42(9H, s).

EXAMPLE 5(61)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(phenylcarbonyl)tetrazol-1-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.47 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.42 (2H, d,J=7.0 Hz), 7.70 (1H, t, J=7.0 Hz), 7.54 (2H, t, J=7.0 Hz), 7.46-7.29(5H, m), 6.12-5.74 (3H, m), 5.20 (2H, s), 4.78 (1H, m), 2.97 and 2.71(each 1H, each dd, J=17.5, 5.0 Hz), 1.36 (9H, s).

EXAMPLE 5(62)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-6-fluorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.74 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.46-7.30 (5H,m), 7.25-7.18 (2H, m), 7.10-6.95 (1H, m), 5.94 (1H, d, J=8.6 Hz), 5.77(1H, d, J=17.8 Hz), 5.58 (1H, d, J=17.8 Hz), 5.16 (2H, s), 4.70-4.55(1H, m), 4.44 (2H, s), 2.99 (1H, dd, J=17.4, 4.5 Hz), 2.68 (1H, dd,J=17.4, 4.8 Hz), 1.41 (9H, s).

EXAMPLE 5(63)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-6-fluorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.51 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.50-7.30(5H, m),7.30-7.16 (2H, m), 7.10-6.94 (1H, m), 5.88 (1H, d, J=9.1 Hz), 5.68 (1H,d, J=18.7 Hz), 5.52 (1H, d, J=18.7 Hz), 5.19 (2H, s), 4.70-4.55(1H, m),3.10 (1H, dd, J=17.6, 4.6 Hz), 2.76 (1H, dd, J=17.6, 4.8 Hz), 1.41 (9H,s).

EXAMPLE 5(64)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(cyclohexylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.42 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.44-7.30 (5H,m), 5.95 (1H, d, J=9.4 Hz), 5.79 (1H, d, J=17.8 Hz), 5.61 (1H, d, J=17.8Hz), 5.18 (2H, s), 4.75-4.60 (1H, m), 3.72-3.50 (1H, m), 3.03 (1H, dd,J=17.4, 4.4 Hz), 2.71 (1H, dd, J=17.4, 4.8 Hz), 2.20-1.30 (10H, m), 1.42(9H, s).

EXAMPLE 5(65)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(cyclohexylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.28 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.48-7.30(5H, m),5.96 (1H, d, J=8.4 Hz), 5.49 (1H, d, J=18.3 Hz), 5.31 (1H, d, J=18.3Hz), 5.19 (2H, s), 4.72-4.57(1H, m), 3.91-3.72 (1H, m), 3.06 (1H, dd,J=17.6, 4.3 Hz), 2.70 (1H, dd, J=17.6, 4.9 Hz), 2.20-1.20 (10H, m), 1.43(9H, s).

EXAMPLE 5(66)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methoxyphenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.50 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.56 (2H, d,J=8.9 Hz), 7.45-7.30 (5H, m), 6.90 (2H, d, J=8.9 Hz), 5.93 (1H, d, J=9.2Hz), 5.75 (11H, d, J=17.8 Hz), 5.58 (1H, d, J=17.8 Hz), 5.16 (2H, s),4.72-4.55 (1H, m), 3.81 (3H, s), 2.97 (1H, dd, J17.3, 4.3 Hz), 2.68 (1H,dd, J=17.3, -4.9 Hz), 1.41 (9H, s).

EXAMPLE 5(67)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methoxyphenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.51 (2H, d,J=8.9 Hz), 7.45-7.32 (5H, m), 6.90 (2H, d, J=8.9 Hz), 5.97 (1H, d, J=9.2Hz), 5.57 (1H, d, J=18.4 Hz), 5.40 (1H, d, J=18.4 Hz), 5.20 (2H, s),4.71-4.55 (1H, m), 3.81 (3H, s), 3.05 (1H, dd, J=17.5, 4.4 Hz), 2.75(1H, dd, J=17.5, 4.9 Hz), 1.43 (9H, s).

EXAMPLE 5(68)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.52 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.51-7.16 (9H,m), 5.93 (1H, d, J=9.4 Hz), 5.84 (1H, d, J=17.8 Hz), 5.66 (1H, d, J=17.8Hz), 5.18 (2H, s), 4.73-4.54 (1H, m), 3.03 (1H, dd, J=17.4 and 4.8 Hz),2.71 (1H, dd, 17.4 and 4.6 Hz), 1.42 (9H, s).

EXAMPLE 5(69)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.40 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.58-7.00 (9H,m), 5.95 (1H, d, J=9.0 Hz), 5.67 (J=18.4 Hz), 5.50 (1H, d, J=18.4 Hz),5.20 (2H, s), 4.74-4.52 (1H, m), 3.05 (1H, dd, J=17.6 and 4.2 Hz), 2.71(1H, dd, 17.6 and 5.0 Hz), 1.41 (9H, s).

EXAMPLE 5(70)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.30 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 7.48 (1H, d,J=2.2 Hz), 7.46-7.31 (6H, m), 7.23 (1H, dd, J=8.4 and 2.2 Hz), 5.93 (1H,d, J=9.0 Hz), 5.84 (1H, d, J=17.8 Hz), 5.66 (1H, d, J=17.8 Hz), 5.18(2H, s), 4.75-4.52 (1H, m), 3.03 (1H, dd, J=17.6 and 4.4 Hz 2.71 (1H,dd, J=17.6 and 4.8 Hz), 1.42 (9H, s).

EXAMPLE 5(71)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.23 (hexane:ethyl acetate=4:1); NMR (CDCl₃): δ 7.53 (1H, d,J=8.4 Hz), 7.47 (1H, d, J=2.4 Hz), 7.45-7.32 (5H, m), 7.27 (1H, dd,J=8.4 and 2.4 Hz), 5.94 (1H, d, J=9.6 Hz), 5.68 (1H, d, J=18.6 Hz), 5.51(1H, d, J=18.6 Hz), 5.20 (2H, s), 4.76-4.52 (1H, m), 3.07 (1H, dd,J=17.6 and 4.6 Hz), 2.72 (1H, dd, J=17.6 and 4.6 Hz), 1.41(9H, s).

EXAMPLE 5(72)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-6-methylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.71 (benzene:diethylether=2:1); NMR (CDCl₃): δ 7.39-7.20 (8H,m), 5.92 (1H, d, J=8.8 Hz), 5.74 (1H, d, J=17.4 Hz), 5.55 (1H, d, J=17.4Hz), 4.65-4.55 (1H, m), 3.00 (1H, dd, J=4.4, 17.4 Hz), 2.69 (1H, dd,J=4.6, 17.4 Hz), 2.52 (3H, s), 1.40 (9H, s).

EXAMPLE 5(73)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-6-methylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.55 (benzene diethylether=2:1); NMR (CDCl₃): δ 7.43-7.23 (8H,m), 5.97 (1H, d, J=9.4 Hz), 5.66 (1H, d, J=18.6 Hz), 5.49 (1H, d, J=18.6Hz), 4.70-4.60 (1H, m), 3.08 (1H, dd, J=4.4, 17.2 Hz), 2.74 (1H, dd,J=4.6, 17.2 Hz), 2.58 (3H, s), 1.43 (9H, s).

EXAMPLE 5(74)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethylphenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.59 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.60 (s, 4H),7.38 (s, 5H), 6.0-5.6 (m, 3H), 5.18 (s, 2H), 4.7-4.6 (m, 1H), 3.05 (dd,J=4.3, 17.5 Hz, 1H), 2.72 (dd, J=4.8, 17.5 Hz, 1H), 1.42 (s, 9H).

EXAMPLE 5(75)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethylphenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.61 (s, 4H),7.38 (s, 5H), 6.0-5.9 (m, 1H), 5.7-5.4 (m, 2H), 5.20 (s, 2H), 4.7-4.6(m, 1H), 3.07 (dd, J=4.3, 17.6 Hz, 1H), 2.71 (dd, J=4.0, 17.5 Hz, 1H),1.41 (s, 9H).

EXAMPLE 5(76)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(naphthalen-2-ylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.47 (hexane:ethyl:acetate=7:3); NMR (CDCl₃): δ 8.08 (1H, d,J=1.5 Hz), 7.87-7.73 (3H, m), 7.62-7.43 (3H, m), 7.41-7.25 (5H, m), 5.93(1H, d, J=8.6 Hz), 5.79 (1H, d, J=17.7 Hz), 5.62 (1H, d, J=17.7 Hz),5.15 (2H, s), 4.71-4.56 (1H, m), 3.00 (1H, dd, J=17.5, 4.4 Hz), 2.69(1H, dd, J=17.5, 4.9 Hz), 1.39 (9H, s).

EXAMPLE 5(77)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(naphthalen-2-ylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.35 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 8.06 (1H, s),7.88-7.75 (3H, m), 7.61-7.46 (3H, m), 7.43-7.30 (5H, m), 5.92 (1H, d,J=8.8 Hz), 5.59 (1H, d, J=18.3 Hz), 5.44 (1H, d, J=18.3 Hz), 5.17 (2H,s), 4.65-4.52 (1H, m), 2.98 (1H, dd, J=17.5, 4.4 Hz), 2.66 (1H, dd,J=17.5, 4.9 Hz), 1.42 (9H, s).

EXAMPLE 5(78)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.49 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.51 (2H, d,J=8.6 Hz), 7.45-7.30 (7H, m), 5.94 (1H, d, J=8.8 Hz), 5.78 (1H, d,J=17.8 Hz), 5.60 (1H, d, J=17.8 Hz), 5.16 (2H, s), 4.70-4.56 (1H, m),3.01 (1H, dd, J=17.4, 4.4 Hz), 2.69 (1H, dd, J=17.4, 4.8 Hz), 1.41 (9H,s), 1.30 (9H, s).

EXAMPLE 5(79)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.34 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.47 (2H, d,J=8.7 Hz), 7.42-7.30 (7H, m), 5.95 (1H, d, J=9.2 Hz), 5.57 (1H, d,J=18.4 Hz), 5.41 (1H, d, J=18.4 Hz), 5.19 (2H, s), 4.68-4.53 (1H, m),3.03 (1H, dd, J=17.4, 4.4 Hz), 2.69 (1H, dd, J=17.4, 4.9 Hz), 1.42 (9H,s), 1.30 (9H, s).

EXAMPLE 5(80)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethyloxyphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.31 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.7-7.5 (m, 2H),7.5-7.3 (m, 5H), 7.3-7.2 (m, 2H), 5.94 (d, J=8.5 Hz, 1H), 5.63 (d,J=18.4 Hz, 1H), 5.46 (d, J=18.4 Hz, 1H), 5.20 (s, 2H), 4.7-4.6 (m, 1H),3.10 (dd, J=4.4, 17.6 Hz, 1H), 2.71 (dd, J=4.9, 17.6 Hz, 1H), 1.42 (s,9H).

EXAMPLE 5(81)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethyloxyphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.37 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.7-7.5 (m, 2H),7.5-7.3 (m, 5H), 7.3-7.2 (m, 2H), 6.0-5.9 (m, 1H), 5.86 (d, J=17.7 Hz,1H), 5.68 (d, J=17.7 Hz, 1H), 5.17 (s, 2H), 4.7-4.6 (m, l H), 3.00 (dd,J=4.4, 17.5 Hz, 1H), 2.70 (dd, J=4.8, 17.5 Hz, 1H), 1.41 (s, 9H).

EXAMPLE 5(82)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.55 (benzene:diethylether=10:1); NMR (CDCl₃): δ 7.51-7.35 (7H,m), 5.92 (1H, d, J=8.8 Hz), 5.78 (1H, d, J=17.8 Hz), 5.59 (1H, d, J=17.8Hz), 5.17 (2H, s), 4.63-4.60 (1H, m), 3.08 (1H, dd, J=4.8, 17.6 Hz),2.71 (1H, dd, J=5.0, 17.6 Hz), 1.41 (9H, s).

EXAMPLE 5(83)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.37 (benzene:diethylether=10:1); NMR (CDCl₃): δ 7.53-7.33 (7H,m), 5.98 (1H, d, J=9.4 Hz), 5.70 (1H, d, J=18.4 Hz), 5.54 (1H, d, J=18.4Hz), 5.21(2H, s), 4.76-4.64 (1H, m), 3.12 (1H, dd, J=4.4, 17.6 Hz), 2.76(1H, dd, J=5.0, 17.6 Hz), 1.43 (9H, s).

EXAMPLE 5(84)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-dimethylphenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.53 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.49 (1H, d,J=7.9 Hz), 7.45-7.30 (5H, m), 7.11 (1H, s), 7.01 (1H, d, J=7.9 Hz), 5.94(1H, d, J=9.1 Hz), 5.76 (1H, d, J=17.8 Hz), 5.57 (1H, d, J=17.8 Hz),5.16 (2H, s), 4.72-4.55 (1H, m), 3.01 (1H, dd, J=17.8, 4.4 Hz), 2.68(1H, dd, J=17.8, 4.7 Hz), 2.39 (3H, s), 2.33 (3H, s), 1.41 (9H, s).

EXAMPLE 5(85)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-dimethylphenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.36 (hexane:ethyl acelate=7:3); NMR (CDCl₃): δ 7.46-7.31 (6H,m), 7.13 (1H, s), 7.02 (1H, d, J=7.7 Hz), 5.96 (1H, d, J=9.2 Hz), 5.56(1H, d, J=18.4 Hz), 5.39 (1H, d, J=8.4 Hz), 5.20 (2H, s), 4.70-4.54 (1H,m), 3.05 (1H, dd, J=17.5, 4.4 Hz), 2.70 (1H, dd, J=17.5, 4.8 Hz), 2.37(3H, s), 2.32 (3H, s), 1.42 (9H, s).

EXAMPLE 5(86)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,5-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.72 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.55-7.30 (6H,m), 7.30-7.17 (2H, m), 5.94 (1H, d, J=9.0 Hz), 5.87 (1H, d, J=17.5 Hz),5.69 (1H, d, J=17.5 Hz), 5.18 (2H, s), 4.73-4.59 (1H, m), 3.05 (1H, dd,J=17.6, 4.0 Hz), 2.71 (1H, dd, J=17.6, 4.8 Hz), 1.42 (9H, s).

EXAMPLE 5(87)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,5-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.64 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.53 (1H, d,J=7.2 Hz), 7.45-7.32 (5H, m), 7.30-7.24 (2H, m), 5.94 (1H, d, J=9.2 Hz),5.69 (1H, d, J=18.3 Hz), 5.52 (1H, d, J=18.3 Hz), 5.20 (2H, s),4.74-4.58 (1H, m), 3.08 (1H, dd, J=17.5, 4.3 Hz), 2.72 (1H, dd, J=17.5,4.8 Hz), 1.42 (9H, s).

EXAMPLE 5(88) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-bromophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.35 (hexane:ethyl acetate=4:1).

EXAMPLE 5(89) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-bromophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.31 (hexane:ethyl acetate=3:1).

EXAMPLE 5(90)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.47 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.42-7.29 (5H,m), 7.27 (2H, d, J=1.4 Hz), 5.92 (1H, d, J=8.8 Hz), 5.75 (1H, d, J=17.6Hz), 5.57 (1H, d, J=17.6 Hz), 5.16 (2H, s), 4.70-4.55 (1H, m), 3.00 (1H,dd, J=17.4, 4.3 Hz), 2.69 (1H, dd, J=17.4, 4.8 Hz), 2.34 (3H, s), 1.42(9H, s).

EXAMPLE 5(91)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.34 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.45-7.31 (5H,m), 7.26 (2H, s), 5.98 (1H, d, J=9.1 Hz), 5.67 (1H, d, J=18.4 Hz), 5.50(1H, d, J=18.4 Hz), 5.21 (2H, s), 4.75-4.62 (1H, m), 3.09 (1H, dd,J=17.5, 4.5 Hz), 2.74 (1H, dd, J=17.5, 4.8 Hz), 2.34 (3H, s), 1.43 (9H,s).

EXAMPLE 5(92)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3,4-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.72 (benzene:diethylether=2:1); NMR (CDCl₃): δ 7.65 (1H, d,J=1.8 Hz), 7.45-7.33 (7H, m), 5.94 (1H, d, J=9.6 Hz), 5.83 (1H, d,J=18.0 Hz), 5.65 (1H, d, J=18.0 Hz), 5.17 (2H, s), 4.70-4.61 (1H, m),3.04 (1H, dd, J=4.2, 17.4 Hz), 2.72 (1H, dd, J=4.6, 17.4 Hz), 1.41 (9H,s).

EXAMPLE 5(93)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3,4-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.53 (benzene:diethylether=2:1); NMR (CDCl₃): δ 7.65 (1H, d,J=2.0 Hz), 7.47-7.34 (7H, m), 5.94 (1H, d, J=8.6 Hz), 5.63 (1H, d,J=18.6 Hz), 5.47 (1H, d, J=18.6 Hz), 5.20 (2H, s), 4.69-4.60 (1H, m),3.09 (1H, dd, J=4.4, 17.6 Hz), 2.75 (1H, dd, J=5.0, 17.6 Hz), 1.43 (9H,s).

EXAMPLE 5(94) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-bromotetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.26 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.39 (5H, m),5.93 (1H, d, J=10.2 Hz), 5.86 (1H, d, J=17.6 Hz), 5.68 (1H, d, J=17.6Hz), 5.18 (2H, s), 4.78-4.55 (1H, m), 3.04 (1H, dd, J=17.4 Hz, and 4.6Hz), 2.72 (1H, dd, J=17.4 Hz and 4.8 Hz), 1.43 (9H, s).

EXAMPLE 5(95)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-nitrophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.40 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.24-8.09 (2H,m), 7.62-7.48 (2H, m), 7.45-7.28 (5H, m), 5.94 (1H, d, J=8.4 Hz), 5.91(1H, d, J=17.8 Hz), 5.72 (1H, d, J=17.8 Hz), 5.18 (2H, s), 4.78-4.58(1H, m), 3.06 (1H, dd, J=17.6 and 4.4 Hz), 2.73 (1H, dd, J=17.6 and 4.8Hz), 1.42 (9H, s).

EXAMPLE 5(96)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-nitrophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.23 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.26-8.11 (2H,m), 7.69-7.50 (2H, m), 7.46-7.28 (5H, m), 5.90 (1H, d, J=9.0 Hz), 5.68(1H, d, J=18.2 Hz), 5.51 (1H, d, J=18.2 Hz), 5.19 (2H, s), 4.75-4.48(1H, m), 3.06 (1H, dd, J=17.6 and 4.4 Hz), 2.71 (1H, dd, J=17.6 and 5.0Hz), 1.41 (9H, s).

EXAMPLE 5(97)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(naphthalen-1-ylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.77 (hexane:ethyl:acetate=1:1); NMR (CDCl₃): δ 8.39 (1H, d,J=7.0 Hz), 7.94-7.85 (3H, m), 7.59-7.43 (3H, m), 7.40-7.30 (5H, m), 5.89(1H, d, J=9.0 Hz), 5.70 (1H, d, J=18.0 Hz), 5.52 (1H, d, J=18.0 Hz),5.13 (2H, s), 4.71-4.56 (1H, m), 2.96 (1H, dd, J=17.0, 4.0 Hz), 2.65(1H, dd, J=17.0, 5.0 Hz), 1.38 (9H, s).

EXAMPLE 5(98)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(naphthalen-1-ylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.70 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.32 (1H, d,J=8.0 Hz), 7.96-7.86 (3H, m), 7.64-7.47 (3H, m), 7.44-7.31 (5H, m), 5.92(1H, d, J=9.0 Hz), 5.59 (1H, d, J=18.0 Hz), 5.43 (1H, d, J=18.0 Hz),5.19 (2H, s), 4.65-4.52 (1H, m), 3.02 (1H, dd, J=17.0, 4.0 Hz), 2.69(1H, dd, J=17.0, 4.0 Hz), 1.42 (9H, s).

EXAMPLE 5(99)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-di-t-butylphenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.48 (benzene:diethylether=8:1); NMR (CDCl₃): δ 7.50 (1H, d,J=2.2 Hz), 7.44 (1H, d, J=8.2 Hz), 7.38-7.35 (5H, m), 7.17 (1H, dd,J=2.2 and 8.2 Hz), 5.94 (1H, d, J=8.4 Hz), 5.76 and 5.59 (each 1H, eachd, J=17.4 Hz), 5.16 (2H, s), 4.69-4.59 (1H, m), 2.99 (1H, dd, J=4.6 and17.4 Hz), 2.69 (1H, dd, J=4.8 and 17.4 Hz), 1.53 (9H, s), 1.41 (9H, s),1.31 (9H, s).

EXAMPLE 5(100)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-di-t-butylphenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.31 (benzene:diethylether=8:1); NMR (CDCl₃): δ 7.52 (1H,d-like), 7.41-7.34 (5H, m), 7.28-7.16 (2H, m), 5.95 (1H, d, J=8.8 Hz),5.60 and 5.43 (each 1H, each d, J=18.4 Hz), 5.19 (2H, s), 4.69-4.59 (1H,m), 3.06 (1H, dd, J=4.6 and 17.4 Hz), 2.71 (1H, dd, J=4.6 and 17.4 Hz),1.51 (9H, s), 1.42 (9H, s), 1.31 (9H, s).

EXAMPLE 5(101)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imidazol-1-ylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.50 (chloroform:methanol=10:1); NMR (CDCl₃): δ 7.62 (1H, s),7.40-7.30 (5H, m), 7.07 (1H, s), 7.05 (1H, s), 5.88 (1H, m), 5.84 (1H,d, J=18 Hz), 5.66 (1H, d, J=18 Hz), 5.39 (2H, 5.17 (2H, s), 4.64 (1H,m), 3.03 (1H, dd, J=4.4, 17 Hz), 2.71 (1H, dd, J=4.6, 17 Hz), 1.42 (9H,s).

EXAMPLE 5(102)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imidazol-1-ylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.44 (chloroform:methanol=10:1); NMR (CDCl₃): δ 7.68 (1H, s),7.40-7.30 (5H, m), 7.08 (1H, s), 7.00 (1H, m), s), 5.84 (1H, m),5.60-5.26 (4H, m), 5.39 (2H, s), 5.18 (2H, s), 4.60 (1H, m), 3.10 (1H,dd, J=4.8, 18 Hz), 2.80 (1H, dd, J=5.0, 18 Hz), 1.42 (9H, s).

EXAMPLE 5(103)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methoxyphenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.53 (benzene:diethylether=2:1); NMR (CDCl₃): δ 7.48-7.30 (7H,m), 6.98-6.90 (2H, m), 5.93 (1H, d, J=9.6 Hz), 5.78 (1H, d, J=17.8 Hz),5.60 (1H, d, J=17.8 Hz), 5.16 (2H, s), 4.89-4.60 (1H, m), 3.81 (3H, s),3.00 (1H, dd, J=4.4, 17.4 Hz), 2.70 (1H, dd, J=4.8, 17.4 Hz), 1.41 (9H,s).

EXAMPLE 5(104)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methoxyphenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.38 (benzene:diethylether=2:1); NMR (CDCl₃): δ 7.52-7.31 (7H,m), 6.99-6.85 (2H, m), 5.96 (1H, d, J=8.8 Hz), 5.64 (1H, d, J=18.2 Hz),5.45 (1H, d, J=18.2 Hz), 5.19 (2H, s), 4.64-4.55 (1H, m), 3.75 (3H, s),3.01 (1H, dd, J=4.4, 17.4 Hz), 2.70 (1H, dd, J=4.8, 17.4 Hz), 1.42 (9H,s).

EXAMPLE 5(105)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.59 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.40-7.30 (5H,m), 6.72 (2H, s), 5.95 (1H, d, J=8.8 Hz), 5.72 (1H, d, J=18 Hz), 5.57(1H, d, J=18 Hz), 5.16 (2H, s), 4.63 (1H, m), 3.02-2.93 (7H, m), 2.69(1H, dd, J=4.6, 17 Hz), 1.41 (9H, s).

EXAMPLE 5(106)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.50 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.42-7.30 (5H,m), 6.69 (2H, s), 5.99 (1H, d, J=8.8 Hz), 5.62 (1H, d, J=18 Hz), 5.47(1H, d, J=18 Hz), 5.20 (2H, s), 4.65 (1H, m), 3.12-2.98 (7H, m), 2.72(1H, dd, J=4.8, 17 Hz), 1.43 (9H, s).

EXAMPLE 5(107)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-2-yl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.27 (benzene:diethylether=8:1); NMR (CDCl₃): δ 7.40-7.32 (5H,m), 7.19-7.16 (1H, m), 6.94-6.90 (2H, m), 5.97 (1H, d, J=8.4 Hz), 5.80and 5.63 (each 1H, each d, J=17.6 Hz), 5.17 (2H, s), 4.71-4.62 (1H, m),4.46 (2H, s), 3.00 (1H, dd, J=4.6 and 17.4 Hz), 2.71 (1H, dd, J=4.8 and17.4 Hz), 1.42 (9H, s).

EXAMPLE 5(108)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-2-yl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.12 (benzene:diethylether=8:1); NMR (CDCl₃): δ 7.37 (5H, m),7.22-7.19 (1H, m), 6.95-6.92 (2H, m), 5.84 (1H, d, J=8.4 Hz), 5.45 and5.34 (each 1H, each d, J=18.6 Hz), 5.16 (2H, s), 4.62-4.53 (1H, m), 4.43and 4.27 (each 1H, each d, J=16.6 Hz), 3.06 (1H, dd, J=4.4 and 17.6 Hz),2.74 (1H, dd, J=4.8 and 17.6 Hz), 1.44 (9H, s).

EXAMPLE 5(109)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-3-yl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.23 (benzene:diethylether=8:1); NMR (CDCl₃): δ 7.40-7.31 (5H,m), 7.28-7.24 (1H, m), 7.12-7.10 (1H, m), 7.03 (1H, dd, J=1.2 and 5.0Hz), 5.97 (1H, d, J=9.2 Hz), 5.80 and 5.62 (each 1H, each d, J=17.6 Hz),5.17 (2H, s), 4.71-4.62 (1H, m), 4.28 (2H, s), 3.00 (1H, dd, J=4.4 and17.6 Hz), 2.71 (1H, dd, J=5.0 and 17.6 Hz), 1.42 (9H, s).

EXAMPLE 5(110)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-3-yl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.09 (benzene:diethylether=8:1); NMR (CDCl₃): δ 7.40-7.33 (5H,m), 7.31-7.27 (1H, m), 7.18 (1H, brs), 6.94-6.91 (1H, m), 5.82 (1H, d,J=8.8 Hz), 5.35 (2H, s), 5.16 (2H, s), 4.59-4.50 (1H, m), 4.24 and 4.07(each 1H, each d, J=16.2 Hz), 3.05 (1H, dd, J=4.4 and 17.4 Hz), 2.73(1H, dd, J=5.0 and 17.4 Hz), 1.44 (9H, s).

EXAMPLE 5(111)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-imidazol-1-ylpropyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.44 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.49 (1H, s),7.40-7.30 (5H, m), 7.05 (1H, s), 6.94 (1H, s), 6.10 (1H, d, J=8.8 Hz),5.81 (1H, d, J=18 Hz), 5.64 (1H, d, J=18 Hz), 2H, s), 4.67 (1H, m), 4.03(2H, t, J=7.0 Hz), 3.02 (1H, dd, J=4.6, 17 Hz), 2.90 (2H, t, J=7.0 Hz),2.72 (1H, dd, J=5.0, 17 Hz), 2.27 (2H, m), 1.42 (9H, s).

EXAMPLE 5(112)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-imidazol-1-ylpropyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.36 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.45 (1H, s),7.40-7.30 (5H, m), 7.04 (1H, s), 6.92 (1H, s), 6.10 (1H, d, J=8.8 Hz),5.46 (2H, s), 5.18 (2H, s), 4.60 (1H, m), 4.09 (2H, t, J=6.8 Hz), 3.03(1H, dd, J=4.4, 18 Hz), 2.78 (1H, dd, J=5.4, 18 Hz), 2.57 (2H, t, J=6.8Hz), , 2.27 (2H, m), 1.41 (9H, s).

EXAMPLE 5(113)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,3-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.60 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.44-7.11 (8H,m), 5.94 (1H, d, J=10.8 Hz), 5.86 (1H, d, J=17.8 Hz), 5.68 (1H, d,J=17.8 Hz), 4.73-4.62 (1H, m), 3.04 (1H, dd, J=4.0, 17.2 Hz), 2.73 (1H,dd, J=4.8, 17.2 Hz), 1.42 (9H, s).

EXAMPLE 5(114)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,3-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.49 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.48-7.15 (8H,m), 5.94 (1H, d, J=10.6 Hz), 5.69 (1H, d, J=18.4 Hz), 5.52 (1H, d,J=18.4 Hz), 4.73-4.63 (1H, m), 3.06 (1H, dd, J=4.4, 17.6 Hz), 2.73 (1H,dd, J=4.8, 17.6 Hz), 1.41 (9H, s).

EXAMPLE 5(115)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethylphenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.56 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.37 (5H, s),7.25-7.10 (3H, m), 5.91 (1H, d, J=9.1 Hz), 5.73 (1H, d, J=17.8 Hz), 5.54(1H, d, J=17.8 Hz), 5.16 (2H, s), 4.70-4.55 (1H, m), 2.99 (1H, dd,J=17.5, 4.5 Hz), 2.67 (1H, dd, J=17.5, 4.8 Hz), 2.48 (6H, s), 1.41 (9H,s).

EXAMPLE 5(116)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethylphenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.44 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.45-7.35 (5H,m), 7.31-7.14 (3H, m), 5.96 (1H, d, J=9.1 Hz), 5.56 (1H, d, J=18.5 Hz),5.38 (1H, d, J=18.5 Hz), 5.21 (2H, s), 4.70-4.54 (1H, m), 3.06 (1H, dd,J=17.5, 4.4 Hz), 2.71 (1H, dd, J=17.5, 4.9 Hz), 2.42 (6H, s), 1.42 (9H,s).

EXAMPLE 5(117)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.65 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.46 (1H, d,J=2.1 Hz), 7.43-7.30 (6H, m), 7.25 (1H, dd, J=8.3, 2.1 Hz), 5.94 (1H, d,J=9.3 Hz), 5.82(1H, d, J=17.8 Hz), 5.64 (1H, d, J=17.8 Hz), 5.17 (2H,s), 4.73-4.58 (1H, m), 3.02 (1H, dd, J=17.4, 4.4 Hz), 2.70 (1H, dd,J=17.4, 4.9 Hz), 1.42 (9H, s), 1.30 (9H, s).

EXAMPLE 5(118)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.55 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.53 (1H, d,J=8.4 Hz), 7.45 (1H, d, J=2.2 Hz), 7.43-7.33 (5H, m), 7.29 (1H, dd,J=8.4, 2.2 Hz), 5.96 (1H, d, J=9.2 Hz), 5.67 (1H, d, J=18.4 Hz), 5.49(1H, d, J=18.4 Hz), 5.20 (2H, s), 4.72-4.60 (1H, m), 3.05 (1H. dd,J=17.5, 4.4 Hz), 2.71 (1H, dd, J=17.5, 4.9 Hz), 1.43 (9H, s), 1.30 (9H,s).

EXAMPLE 5(119)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,2,6,6-tetramethylpiperidin-2-ylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.52 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.40-7.30 (5H,m), 5.98 (1H, d, J=8.6 Hz), 5.79 (1H, d, J=18 Hz), 5.61 (1H, d, J=18Hz), 5.17 (2H, s), 4.66 (1H, m), 4.00 (2H, s), 2.99 (1H, dd, J=4.2, 17Hz), 2.70 (1H, dd, J=4.6, 17 Hz), 1.60-1.44 (6H, m), 1.42 (9H, s), 1.07(12H, s).

EXAMPLE 5(120)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,2,6,6-tetramethylpiperidin-1-ylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.31 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.40-7.30 (5H,m), 6.04 (1H, d, J=9.0 Hz), 5.95 (1H, d, J=18 Hz), 5.76 (1H, d, J=18Hz), 5.20 (2H, s), 4.68 (1H, m), 4.01 (2H, s), 3.05 (1H, dd, J=4.4, 17Hz), 2.73 (1H, dd, J=4.8, 17 Hz), 1.62-1.46 (6H, m), 1.43 (9H, s), 0.99and 0.94 (total 12H, each s).

EXAMPLE 5(121) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(N-phenyl-N-methylamino)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.17 (benzene:diethylether=8:1); NMR (CDCl₃): δ 7.47-7.31 (9H,m), 7.12-7.05 (1H, m), 5.96 (1H, d-like), 5.66 and 5.49 (each 1H, eachd, J=17.6 Hz), 5.16 (2H, s), 4.70-4.60 (1H, m), 3.56 (3H, s), 3.00 (1H,dd, J=4.4 and 17.4 Hz), 2.70 (1H, dd, J=5.0 and 17.4 Hz), 1.42 (9H, s).

EXAMPLE 5(122)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(N-phenyl-N-methylamino)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.04 (benzene diethylether=8:1); NMR (CDCl₃): δ 7.41-7.19 (8H,m), 6.98-6.94 (2H, m), 5.60 (1H, d-like), 5.08 (2H, s), 4.89 and 4.69(each 1H, each d, J=18.6 Hz), 4.11-3.99 (1H, m), 3.49 (3H, s), 2.74 (1H,dd, J=4.6 and 17.4Hz), 2.49 (1H, dd, J=4.8 and 17.4 Hz), 1.40 (9H, s).

EXAMPLE 5(123)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-diisopropylphenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.41 (benzene:diethylether=8:1); NMR (CDCl₃): δ 7.46-7.31 (6H;m), 7.25-7.21 (2H, m), 5.91 (1H, d, J=9.4 Hz), 5.71 and 5.52 (each 1H,each d, J=18.2 Hz), 5.15 (2H, s), 4.65-4.55 (1H, m), 3.84-3.70 (2H, m),2.97 (1H, dd, J=4.4 and 17.4 Hz), 2.66 (1H, dd, J=5.0 and 17.4 Hz), 1.39(9H, s), 1.17 (12H, d, J=6.8 Hz).

EXAMPLE 5(124)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-diisopropylphenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.24 (benzene:diethylether=8:1); NMR (CDCl₃): δ 7.50-7.35 (6H,m), 7.28-7.25 (2H, m), 5.98 (1H, d-like), 5.60 and 5.44 (each 1H, eachd, J=18.2 Hz), 5.21 (2H, s), 4.75-4.64 (1H, m), 3.60-3.47 (2H, m), 3.11(1H, dd, J=4.4 and 17.6 Hz), 2.75 (1H, dd, J=5.0 and 17.6 Hz), 1.44 (9H,s), 1.19 and 1.16 (each 6H, each d, J=6.8 Hz).

EXAMPLE 5(125)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methyl-4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.52 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.50 (1H, d,J=8.2 Hz), 7.43-7.3,2 (5H, m), 7.29 (1H, d, J=2.2 Hz), 7.21 (1H, dd,J=8.2, 2.2 Hz), 5.94 (1H, d, J=9.0 Hz), 5.77(1H, d, J=17.8 Hz), 5.58(1H, d, J=17.8 Hz), 5.16 (2H, s), 4.72-4.56 (1H, m), 3.00 (1H, dd,J=17.3, 4.4 Hz), 2.69 (1H, dd, J=17.3, 4.8 Hz), 2.43 (3H, s), 1.41 (9H,s), 1.30 (9H, s).

EXAMPLE 5(126)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methyl-4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.42 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.55-7.15 (8H,m), 5.94 (1H, d, J=9.0 Hz), 5.57 (1H, d, J=18.6 Hz), 5.40 (1H, d, J=18.6Hz), 5.20 (2H, s), 4.68-4.52 (1H, m), 3.03 (1H, dd, J=17.6, 4.4 Hz),2.69 (1H, dd, J=17.6, 4.8 Hz), 2.41 (3H, s), 1.42 (9H, s), 1.30 (9H, s).

EXAMPLE 5(127)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.63 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.37 (5H, s),7.16 (2H, s), 5.93 (1H, d, J=9.1 Hz), 5.73(1H, d, J=17.7 Hz), 5.55 (1H,d, J=17.7 Hz), 5.15 (2H, s), 4.70-4.56 (1h, m), 2.99 (1H, dd, J=17.3,4.4 Hz), 2.68 (1H, dd, J=17.3, 4.8 Hz), 2.48 (6H, s), 1.41 (9H, s), 1.30(9H, s).

EXAMPLE 5(128)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.50 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.45-7.32 (5H,m), 7.18 (2H, s), 5.97 (1H, d, J=9.2 Hz), 5.57 (1H, d, J=18.5 Hz), 5.39(1H, d, J=18.5 Hz), 5.20 (2H, s), 4.68-4.54 (1H, m), 3.06 (1H, dd,J=17.5, 4.3 Hz), 2.71 (1H, dd, J=17.5, 4.9 Hz), 2.41 (3H, s), 1.43 (9H,s), 1.30 (9H, s).

EXAMPLE 5(129)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.56 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.40-7.30 (5H,m), 6.49 (2h, s), 5.93 (1H, d, J=9.0 Hz), 5.71 (1H, d, J=18 Hz), 5.53(1H, d, J=18 Hz), 5.15 (2H, s), 4.62 (1H, m), 3.02-2.92 (7H, m), 2.67(1H, dd, J=5.0, 17 Hz), 2.44 (6H, s), 1.40 (9H, s);

EXAMPLE 5(130)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.42-7.32 (5H,m), 6.48 (2H, s), 5.96 (1H, d, J=8.8 Hz), 5.51 (1H, d, J=18 Hz), 5.33(1H, d, J=18 Hz), 5.20 (2H, s), 4.61 (1H, m), 3.07-2.96 (7H, m), 2.70(1H, dd, J=4.8, 18 Hz), 2.37 (6H, s), 1.43 (9H, s).

EXAMPLE 5(131)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzoimizazol-2-ylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.16 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 11.70-10.25 (1H,br), 7.73-7.11 (9H, m), 6.36-6.15 (1H, m), 5.90 (1H, d, J=18.6 Hz), 5.67(1H, d, J=18.6 Hz), 5.18 (2H, s), 4.82-4.58 (1H, m), 4.54 (2H, s), 2.96(1H, dd, J=17.2 and 5.0 Hz), 2.72 (1H, dd, J=17.2 and 5.0 Hz), 1.34 (9H,s).

EXAMPLE 5(132)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzoimizazol-2-ylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.11 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 10.80-9.90 (1H,br), 7.94-7.08 (9H, m), 6.05 (1H, d, J=9.8 Hz), 5.73 (2H, brs), 5.15(2H, s), 4.80-4.52 (1H, m), 4.66 (2H, s), 3.03 (1H, dd, J=17.8 and 5.0Hz), 2.70 (1H, dd, J=17.8 and 5.0 Hz), 1.42 (9H, s).

EXAMPLE 5(133)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-isopropylphenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.45 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.50 (2H, d,J=10.6 Hz), 7.40-7.30 (5H, m), 7.23 (2H, d, J=10.6 Hz), 5.94 (1H, d,J=9.0 Hz), 5.79 (1H, d, J=17.6 Hz), 5.61 (1H, d, J=17.6 Hz), 5.17 (2H,s), 4.70-4.60 (1H, m), 3.06-2.83 (2H, m), 2.71 (1H, dd, J=4.8, 17.2 Hz),1.41 (9H, s), 1.24 (6H, d, J=7.0 Hz).

EXAMPLE 5(134)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-isopropylphenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.32 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.49-7.34 (7H,m), 7.23 (2H, d, J=8.4 Hz), 5.96 (1H, d, J=9.0 Hz), 5.58 (1H, d, J=8.4Hz), 5.42 (1H, d, J=18.4 Hz), 5.20 (2H, s), 4.68-4.58 (1H, m), 3.09-2.83(2H, m), 2.69 (1H, dd, J=4.8, 17.6 Hz), 1.43 (9H, s), 1.23 (6H, d, J=6.8Hz).

EXAMPLE 5(135)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzothiazol-2-ylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.60 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.09-7.94 (1H,m), 7.92-7.74 (1H, m), 7.53-7.28 (7H, m), 5.98 (1H, d, J=9.6 Hz), 5.85(1H, d, J=17.8 Hz), 5.68 (1H, d, J=17.8 Hz), 5.17 (2H, s), 4.80 (2H, s),4.74-4.57 (1H, m), 3.01 (1H, dd, J=17.6 Hz and 4.6 Hz), 2.72 (1H, dd,J=17.6 and 4.8 Hz), 1.41 (9H, s).

EXAMPLE 5(136)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzothiazol-2-ylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.54 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.02-7.76 (2H,m), 7.54-7.22 (7H, m), 6.04-5.08 (1H, m), 5.96 (1H, d, J=18.6 Hz), 5.73(1H, d, J=18.6 Hz), 5.12 (2H, s), 4.80-4.51 (3H, m), 3.01 (1H, dd,J=17.6 Hz and 5.0 Hz), 2.74 (1H, dd, J=17.6 and 4.8 Hz), 1.38 (9H, s).

EXAMPLE 5(137)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-2-ylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.70 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.80 (1H, d,J=3.4 Hz), 7.42 (1H, d, J=3.4 Hz), 7.38 (5H, m), 6.00 (1H, d, J=9 Hz),5.87 (1H, d, J=18.0 Hz), 5.70 (1H, d, J=18.0 Hz), 5.20 (2H, m), 5.67(1H, m), 3.03 (1H, dd, J=17.4 Hz, 4.2 Hz), 2.72 (1H, dd, J=17.4 Hz, 4.8Hz), 1.42 (9H, s).

EXAMPLE 5(138)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-2-ylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.56 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.75 (1H, d,J=3.4 Hz), 7.46 (1H, d, J=3.4 Hz), 7.38 (5H, m), 6.00 (1H, d, J=8.8 Hz),5.81 (1H, d, J=18.4 Hz), 5.64 (1H, d, J=18.4 Hz), 5.19 (2H, m), 4.72(1H, m), 3.03 (1H, dd, J=17.6 Hz, 4.2 Hz), 2.74 (1H, dd, J=17.4 Hz, 4.8Hz), 1.42 (9H, s).

EXAMPLE 5(139)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4,6-trichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.48 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.47 (2H, s),7.37 (5H, brs), 5.82 (1H, d, J=8.8 Hz), 5.76 (1H, d, J=17.6 Hz), 5.58(1H, d, J=17.6 Hz), 5.16 (2H, s), 4.70-4.54 (1H, m), 3.06 (1H, dd,J=17.5, 4.4 Hz), 2.69 (1H, dd, J=17.5, 5.0 Hz), 1.41 (9H, s).

EXAMPLE 5(140)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4,6-trichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.31 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.47 (2H, s),7.39 (5H, brs), 5.96 (1H, d, J=8.4 Hz), 5.67 (1H, d, J=18.3 Hz), 5.50(1H, d, J=18.3 Hz), 5.21 (2H, s), 4.75-4.60 (1H, m), 3.01 (1H, dd,J=17.6, 4.3 Hz), 2.74 (1H, dd, J=17.6, 4.9 Hz), 1.43 (9H, s).

EXAMPLE 5(141)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-(1,1-dimethylpropyl)phenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.51 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.42-7.30 (7H,m), 5.92 (1H, d, J=8.8 Hz), 5.76 (1H, d, J=17.7 Hz), 5.57 (1H, d, J=17.7Hz), 5.16 (2H, s), 4.70-4.55 (1H, m), 2.99 (1H, dd, J=17.2, 4.6 Hz),2.69 (1H, dd, J=17.2, 4.6 Hz), 1.63 (2H, q, J=7.5 Hz), 1.41 (9H, s),1.27 (6H, s), 0.72 (3H, t, J=7.5 Hz).

EXAMPLE 5(142)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-(1,1-dimethylpropyl)phenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.42 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.43-7.28 (7H,m), 5.97 (1H, d, J=8.8 Hz), 5.68 (1H, d, J=18.1 Hz), 5.51 (1H, d, J=18.1Hz), 5.21 (2H, s), 4.75-4.60 (1H, m), 3.08 (1H, dd, J=17.6, 4.5 Hz),2.73 (1H, dd, J=17.6, 4.7 Hz), 1.62 (2H, q, J=7.5 Hz), 1.43 (9H, s),1.26 (6H, s), 0.72 (3H, t, J=7.5 Hz).

EXAMPLE 5(143)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1,1-diphenylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.31 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.47-7.15 (15H,m), 5.95 (1H, d, J=8.6 Hz), 5.83 (1H, s), 5.82 (1H, d, J=7.4 Hz), 5.46(1H, d, J=17.4 Hz), 5.16 (2H, s), 4.76-4.56 (1H, m), 3.01 (1H, dd,J=17.4 and 4.4 Hz), 2.70 (1H, dd, J=17.4 and 4.8 Hz), 1.41 (9H, s).

EXAMPLE 5(144)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1,1-diphenylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.21 (hexane:ethyl:acetate=3:1); NMR (CDCl₃): δ 7.46-7.13 (15H,m), 5.72 (1H, d, J=9.0 Hz), 5.55-5.26 (3H, m), 5.15 (2H, s), 4.68-4.45(1H, m), 3.11 (1H, dd, J=17.2 and 3.8 Hz), 2.75 (1H, dd, J=17.2 and 4.6Hz), 1.42 (9H, s).

EXAMPLE 5(145)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-4-fluorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.35 (hexane:ethyl:acetate=3:1); NMR (CDCl₃): δ 7.58 (1H, dd,J=8.8 and 5.8 Hz), 7.48-7.27 (5H, m), 7.27-7.17 (1H, m), 7.07-6.92 (1H,m), 5.95 (1H, d, J=9.2 Hz), 5.81 (1H, d, J=17.6 Hz), 5.63 (1H, d, J=17.6Hz), 5.17 (2H, s), 4.76-4.54 (1H, m), 3.03 (2H, dd, J=17.4 and 4.8 Hz),2.70 (1H, dd, J=17.4 and 5.0 Hz), 1.41 (9H, s).

EXAMPLE 5(146)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-4-fluorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.25 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.68 (1H, dd,J=8.8 and 5.6 Hz), 7.52-7.27 (5H, m), 7.23 (1H, dd, J=8.4 and 2.8 Hz),7.12-6.95 (1H, m), 5.97 (1H, d, J=9.4 Hz), 5.68 (1H, d, J=18.2 Hz), 5.50(1H, d, J=18.2 Hz), 5.20 (2H, s), 4.79-4.52 (1H, m), 3.07 (1H, dd,J=17.6 and 4.4 Hz), 2.73 (1H, dd, J=117.6 and 4.8 Hz), 1.42 (9H, s).

EXAMPLE 5(147)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(5-imidazol-1-ylpentyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.40 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.44 (1H, s),7.48-7.25 (5H, m), 7.03 (1H, s), 6.88 (1H, s), 6.38 (1H, d, J=9.2 Hz),5.79 (1H, d, J=17.6 Hz), 5.62 (1H, d, J=17.6 Hz), 5.18 (2H, s),4.78-4.60 (1H, m), 3.92 (2H, t, J=7.2 Hz), 3.07-2.83 (3H, m), 2.75 (1H,dd, J=17.4 and 5.4 Hz), 1.97-1.57 (6H, m), 1.42 (9H, s).

EXAMPLE 5(148)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(5-imidazol-1-ylpentyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.31 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.46 (1H, s),7.45-7.20 (5H, m), 7.03 (1H, s), 6.89 (1H, s), 6.22 (1H, d, J=8.6 Hz),5.49 (2H, brs), 5.18 (2H, s), 4.72-4.52 (1H, m), 3.93 (2H, t, J=7.2 Hz), 3.12 (1H, dd, J=17.6 and 4.8 Hz), 2.78 (1H, dd, J=17.4 and 5.2 Hz),2.61 (2H, t, J=7.2 Hz), 1.96-1.57 (6H, m), 1.42 (9H, s).

EXAMPLE 5(149)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-dimethylaminoethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.43 (chloroform:methanol=9:1).

EXAMPLE 5(150)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-dimethylaminoethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.43 (chloroform:methanol=9:1).

EXAMPLE 5(151)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-fluorophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.30 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.92-7.76 (2H,m), 7.46-7.28 (5H, m), 7.34 (1H, s), 7.17-7.01 (2H, m), 5.95 (1H, d,J=9.2 Hz), 5.85 (1H, d, J=7.6 Hz), 5.68 (1H, d, J=17.6 Hz), 5.18 (2H,s), 4.77-4.60 (1H, m), 4.73 (2H ,s), 3.02 (1H, dd, J=17.6 and 4.6 Hz),2.72 (1H, dd, J=17.6 and 4.8 Hz), 1.42 (9H, s).

EXAMPLE 5(152)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-fluorophenyl)thiazol-2-ylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.16 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.89-7.68 (2H,m), 7.44-7.24 (5H, m), 7.36 (1H, s), 7.16-7.00 (2H, m), 5.85 (1H, d,J=8.6 Hz), 5.98 (1H, d, J=18.6 Hz), 5.75 (1H, d, J=18.6 Hz), 5.22-4.99(2H, m), 4.76-4.46 (3H, m), 3.00 (1H, dd, J=17.6 and 4.6 Hz), 2.71 (1H,dd, J=17.6 and 4.8 Hz), 1.39 (9H, s).

EXAMPLE 5(153)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-chlorophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.36 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.86-7.74 (2H,m), 7.46-7.28 (8H, m), 5.96 (1H, d, J=9.2 Hz), 5.85 (1H, d, J=17.8 Hz),5.68 (1H, d, J=17.8 Hz), 5.17 (2H, s), 4.78-4.58 (1H, m), 4.73 (2H ,s),3.02 (1H, dd, J=17.4 and 4.4 Hz), 2.72 (1H, dd, J=17.4 and 4.8 Hz), 1.42(9H, s).

EXAMPLE 5(154)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-chlorophenyl)thiazol-2-ylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.20 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.84-7.74 (2H,m), 7.49-7.21 (8H, m), 5.98 (1H, d, J=18.6 Hz), 5.87 (1H, d, J=9.0 Hz),5.75 (1H, d, J=18.6 Hz), 5.14 (1H, d, J=12.2 Hz), 5.06 (1H, d, J=2.2Hz), 4.76-4.44 (3H, m), 3.01 (1H, dd, J=17.6 and 4.6 Hz), 2.72 (1H, dd,J=17.6 and 5.0 Hz), 1.39 (9H, s).

EXAMPLE 5(155)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(3-nitrophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.27 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.76-8.66 (1H,m), 8.30-8.06 (2H, m), 7.66-7.50 (2H, m), 7.46-7.22 (5H, m), 5.97 (1H,d, J=8.8 Hz), 5.87 (1H, d, J=17.6 Hz), 5.70 (1H, d, J=17.6 Hz), 5.18(2H, s), 4.80-4.56 (1H, m), 4.76 (2H, s), 3.03 (1H, dd, J=17.6 and 4.4Hz), 2.73 (1H, dd, J=17.6 and 5.0 Hz), 1.42 (9H, s).

EXAMPLE 5(156)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(3-nitrophenyl)thiazol-2-ylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.18 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.73 (1H, brs),8.23-8.04 (2H, m), 7.64-7.44 (2H, m), 7.44-7.14 (5H, m), 6.06 (1H, d,J=18.8 Hz), 5.94 (I H, d, J=8.0 Hz), 5.76 (1H, d, J=18.8 Hz), 5.08 (2H,brs), 4.77-4.46 (3H, m), 3.09 (1H, dd, J=17.6 and 4.4 Hz), 2.78 (1H, dd,J=17.6 and 5.0 Hz), 1.41 (9H, s).

EXAMPLE 5(157)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethylcarbonylaminophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.64 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.01 (1H, brs),7.53 (4H, brs), 7.37 (5H, brs), 5.96 (1H, d, J=9.0 Hz), 5.81 (1H, d,J=17.8 Hz), 5.63 (1H, d, J=17.8 Hz), 5.16 (2H, s), 4.76-4.52 (1H, m),3.00 (1H, dd, J=17.6 and 4.4 Hz), 2.71 (1H, dd, J=17.6 and 5.0 Hz), 1.41(9H, s).

EXAMPLE 5(158)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethylcarbonylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.08 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 8.81-8.62 (1H,br), 7.65-7.25 (9H, m), 5.94 (1H, d, J=8.8 Hz), 5.62 (1H, d, J=18.4 Hz),5.46 (1H, d, J=18.4 Hz), 5.20 (2H, s), 4.75-4.50 (1H, m), 3.07 (1H, dd,J=18.0 and 4.4 Hz), 2.73 (1H, dd, J=18.0 and 5.2 Hz), 1.43 (9H, s).

EXAMPLE 5(159)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imizazol-4-ylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.35 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.50 (1H, s),7.38-7.30 (5H, m), 6.85 (1H, s), 6.32 (1H, d, J=9.0 Hz), 5.74 (1H, d,J=18 Hz), 5.63 (1H, d, J=18 Hz), 5.14 (2H, s), 4.68 (1H, m), 4.24 (2H,s), 2.93 (1H, dd, J=4;8, 17-Hz), 2.73 (1H, dd, J=5.0, 17 Hz), 1.40 (9H,s).

EXAMPLE 5(160)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imizazol-4-ylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.35 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.41 (1H, s),7.38-7.30 (5H, m), 6.86 (1H, s), 6.43 (1H, d, J=8.8 Hz), 5.74 (1H, d,J=19 Hz), 5.53 (1H, d, J=19 Hz), 5.16 (2H, S), 4.69 (1H, m), 4.11 (2H,s), 2.98 (1H, dd, J=5.0, 17 Hz), 2.76 (1H, dd, J=5.4, 17 Hz), 1.40 (9H,s).

EXAMPLE 6(1)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid

To a solution of compound prepared in example 5(1) (119 mg) in m-cresole(0.9 ml) was added trifluoroacetic acid (9 ml). The reaction mixture wasstirred for 1 h at room temperature. To the reaction mixture was addedtoluene, and then the mixture was concentrated. The residue was purifiedby column chromatography on silica gel (chloroform:methanol:aceticacid=30:1:1) to give the compound of the present invention (68 mg)having the following physical data.

TLC:Rf 0.22 (chloroform:methanol:acetic acid=28:1:1); NMR (CDCl₃): δ7.67 (1H, brs), 7.40-7.00 (8H, m), 6.31 (1H, brs), 5.54 (1H, brd, J=17Hz), 5.34 (1H, d, J=17 Hz), 5.10 (2H, s), 4.52 (1H, brs), 4.24 (2H, brs)2.94 (1H, brd, J=16 Hz), 2.65 (1H, brd, J=16 Hz).

EXAMPLE 6(2)-6(160)

By the same procedure as provided in example 6(1), and if necessary, byknown methods converting the same to a corresponding salt, using thecompound prepared in example 5(2)-5(160), compounds of the presentinvention having the following physical data were obtained.

EXAMPLE 6(2)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.37 (cloroform:methanol:acetic acid=28:1:1); NMR (CDCl₃): δ 8.53(1H, brs), 7.60-7.10 (8H, m), 6.20 (1H, brs), 5.90-5.30 (2H, ,m) 5.08(2H, s), 4.73-4.35) (3H, m), 2.97 (1H, brd, J=17 Hz), 2.69 (1H, bed,J=17 Hz).

EXAMPLE 6(3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoic acid

TLC:Rf 0.44 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.05-7.95 (1H, m), 7.42-7.17 (10H, m), 5.81-5.60 (2H, m), 5.09 (2H, s),4.67-4.52 (1H, m), 4.13 (2H, s), 2.87-2.56 (2H, m).

EXAMPLE 6(4)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-phenylmethyltetrazol-2-yl)pentanoic acid

TLC:Rf 0.60 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.98-7.86 (1H, m), 7.41-7.12 (10H, m), 5.96-5.74 (2H, m), 5.07 (2H, s),4.67-4.50 (1H, m), 4.23 (2H, s), 2.85-2.53 (2H, m).

EXAMPLE 6(5)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methylphenoxy)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.30 (chloroform:methanol:acetic acid=30:1:1); NMR (CDCl₃): δ7.41-7.22 (5H, m), 7.20-7.03 (4H, m), 6.20 (1H, brs), 5.46 (1H, d, J=18Hz), 5.20-4.98 (3H, m), 4.67-4.52 (1H, m), 3.06 (1H, brd, J=18 Hz), 2.74(1H, brd, J=18 Hz), 2.31 (3H, s).

EXAMPLE 6(6)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methylphenoxy)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.34 (chloroform:methanol:acetic acid=18:1:1); NMR (CDCl₃): δ7.43-7.23 (5H, m), 7.22-7.00 (4H, m), 6.06 (1H, brs), 5.57 (1H, d, J=18Hz), 5.38 (1H, d, J=18 Hz), 5.11 (2H, s), 4.72-4.55 (1H, m), 3.05 (1H,brd, J=18 Hz), 2.73 (1H, brd, J=18 Hz), 2.31 (3H, s).

EXAMPLE 6(7)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-t-butylphenoxy)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.38 (chloroform:methanol:acetic acid=30:1:1); NMR (CDCl₃): δ7.35-7.18 (8H, m), 7.15-6.98 (1H, m), 6.30-6.13 (1H, m), 5.48 (1H, d,J=18 Hz), 5.25-4.95 (3H, m), 4.71-4.55 (1H, m), 2.98 (1 H, brd, J=18Hz), 2.77 (1H, brd, J=18 Hz), 1.29 (9H, s).

EXAMPLE 6(8)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-t-butylphenoxy)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=11:1); NMR (CDCl₃): δ7.40-7.16 (8H, m), 7.03 (1H, d, J=8.0 Hz), 5.88 (1H, brs), 5.42 (2H,brs), 5.14 (2H, s), 4.73-4.58 (1H, m), 3.09 (1H, dd, J=18.0, 6.0 Hz),2.76 (1H, dd, J=18.0, 6.0 Hz), 1.29 (9H, s).

EXAMPLE 6(9)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-styryltetrazol-1-yl)pentanoicacid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.14 (1H, d, J=8.0 Hz), 7.85-7.68 (3H, m), 7.50-7.24 (8H, m), 7.16 (1H,d, J=16.2 Hz), 5.90 (2H, s), 5.13 (2H, s), 4.76-4.58 (1H, m), 2.84 (1H,dd, J=16.0, 6.0 Hz), 2.70 (1H, dd, J=16.0, 6.6 Hz).

EXAMPLE 6(10)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-styryltetrazol-2-yl)pentanoicacid

TLC:Rf 0.45 (chloroform:methanol:acetic acid=20 1:1); NMR (DMSO-d₆): δ7.94-7.51 (3H, m), 7.51-7.13 (10H, m), 5.98 (2H, s), 5.09 (2H, s),4.67-4.50 (1H, m), 2.65 (2H, d, J=5.5 Hz).

EXAMPLE 6(11)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-phenylethyltetrazol-1-yl)pentanoic acid

TLC:Rf 0.26 (chloroform:methanol:acetic acid=28:1:1); NMR (DMSO-d₆): δ8.03 (1H, d, J=7.4 Hz), 7.40-7.10 (10H, m), 5.64 (2H, s), 5.07 (2H, s),4.67-4.52 (1H, m), 2.99 (4H, s), 2.80 (1H, dd, J=17.0, 6.0 Hz), 2.66(1H, dd, J=17.0, 6.8 Hz).

EXAMPLE 6(12)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-phenylethyltetrazol-1-yl)pentanoic acid

TLC:Rf 0.42 (chloroform:methanol:acetic acid=28:1:1); NMR (DMSO-d₆): δ7.91 (1H, d, J=7.2 Hz), 7.45 7.08 (10H, m), 5.88 (2H, s), 5.09 (2H, s),4.66-4.50 (1H, m), 3.20-2.96 (4H, m), 2.76 (1H, dd, J=16.8, 6.0 Hz),2.63 (1H, dd, J=16.8, 7.2 Hz).

EXAMPLE 6(13)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-methoxytetrazol-1-yl) pentanoicacid

TLC:Rf 0.25 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 7.55 (1H, m),7.38 (5H, m), 5.55-5.27 (2H, m), 5.08 (2H, s), 4.49 (1H, m), 4.10 (3H ,), 2.56 (2H, m).

EXAMPLE 6(14)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-methoxytetrazol-2-yl) pentanoicacid

TLC:Rf 0.31 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 7.94 (1H, m),7.37 (5H, m), 5.82 (2H, brs), 5.09 (2H, s), 4.60 (1H, m), 4.03 (3H, s),2.88-2.55 (2H, m).

EXAMPLE 6(15) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(N,N-dibenzylamino)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.34 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.01-7.87 (1H, m), 7.42-7.12 (15H, m), 5.80-5.65 (2H, m), 5.70 (2H, s),4.70-4.50 (1H, m), 4.57 (4H, s), 2.90-2.52 (2H, m).

EXAMPLE 6(16)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-trifluoromethyltetrazol-1-yl)pentanoic acid

HPTLC:Rf 0.28 (chloroform:methanol=4:1); NMR (CDCl₃): δ 7.35 (5H, m),5.96 (1H, m), 5.88-5.43 (2H, m), 5.17 (2H, s), 4.70 (1H, m), 4.0 (1H,brs), 3.25-3.03 and 2.96-2.73 (total 2H, m).

EXAMPLE 6(17)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-trifluoromethyltetrazol-2-yl)pentanoic acid

HPTLC:Rf 0.38 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 7.62 (1H, m),7.37 (5H, m), 6.24 (2H, brs), 5.08 (2H, s), 4.56 (1H, m), 2.61 (2H, m).

EXAMPLE 6(18)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(ethoxycarbonylmethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.35 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 7.67 (1H, m),7.36 (5H, m), 5.97 (2H, brs), 5.07 (2H, s), 4.52 (1H, m), 4.19-3.96 (4H,m), 2.60 (2H, d, J=5.0 Hz), 1.20 (3H, t, J=7.0 Hz).

EXAMPLE 6(19)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylthiotetrazol-1-yl) pentanoicacid

TLC:Rf 0.27 (chloroform:methanol:acetic acid=30:1:1); NMR (DMSO-d₆): δ7.99 (1H, m), 7.36 (5H, m), 5.56 (2H, m), 5.10 (2H, s), 4.60 (1H, m),3.20 (2H, q, J=7.5 Hz), 2.-72 (2H, m), 1.31 (3H, t, J=7.5 Hz).

EXAMPLE 6(20)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylthiotetrazol-2-yl) pentanoicacid

TLC:Rf 0.41 (chloroform:methanol:acetic acid=30:1:1); NMR (DMSO-d₆): δ7.98 (1H, m), 7.38 (5H, m), 5.93 (2H, m), 5.09 (2H, s), 4.63 (1H, m),3.19 (2H, q, J=7.5 Hz), 2.73 (2H, m), 1.34 (3H, t, J=7.5 Hz).

EXAMPLE 6(21)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(ethoxycarbonylmethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.56 (chloroform:ethanol:acetic acid=8:1:1); NMR (DMSO-d₆): δ7.66 (1H, m), 7.37 (5H, m), 5.79 (2H, brs), 5.07 (2H, s), 4.49 (1H, m),4.23-3.94 (4H, m), 2.61 (2H, m), 1.18 (3H, t, J=6.5 Hz).

EXAMPLE 6(22) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-((4-chlorophenyl)thiomethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.55 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ7.94 (1H, m), 7.38 (9H, m), 5.90 (2H, m), 5.10 (2H, s), 4.60 (1H, m),4.52 (2H, s), 2.70 (2H, m).

EXAMPLE 6(23) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-((4-chlorophenyl)thiomethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ7.98 (1H, m), 7.38 (9H, m), 5.79 (2H, m), 5.10 (2H, s), 4.60 (1H, m),4.48 (2H, m), 2.74 (2H, m).

EXAMPLE 6(24)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-phenylpropyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.51 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.05-7.90 (1H, m), 7.43-7.09 (10H, m), 6.01-5.78 (2H, m), 5.09 (2H, s),4.68-4.53 (1H, m), 2.90-2.72 and 2.72-2.54 (4H, m), 2.07-1.88 (2H, m).

EXAMPLE 6(25)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-phenylpropyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.38 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.10-8.00 (1H, m), 7.43-7.08 (10H, m), 5.77-5.58 (2H, m), 5.10 (2H, s),4.69-4.53 (1H, m), 2.88-2.54 (4H, m), 2.03-1.92 (2H, m).

EXAMPLE 6(26)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenyloxy)tetrazol-2-yl)pentanoic acid

HPTLC:Rf 0.38 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 7.92 (1H, br),7.67 (2H, d, J=7.5 Hz), 7.51-7.24 (6H, m), 5.88 (2H, br), 5.08 (2H, s),4.59 (1H, m), 2.87-2.54 (2H, m).

EXAMPLE 6(27)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenyloxy)tetrazol-1-yl)pentanoic acid

HPTLC:Rf 0.30 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 8.00 (1H, m),7.79 and 7.58-7.16 (total 8H, m), 5.73 (2H, br), 5.08 (2H, brs), 4.66(1H, m), 2.96-2.60 (2H, m).

EXAMPLE 6(28)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chlorophenyloxymethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.58 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ8.00 (1H, m), 7.38 (8H, m), 7.00 (1H, m), 6.01 (2H, br), 5.50 (2H, s),5.10 (2H, s), 4.64 (1H, m), 2.74 (2H, m).

EXAMPLE 6(29)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chlorophenyloxymethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.53 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ8.08 (1H, m), 7.34 (8H, m), 7.02 (1H, m), 5.88 (2H, br), 5.48 (2H, s),5.01 (2H, s), 4.62 (1H, m), 2.72 (2H, m).

EXAMPLE 6(30)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methoxycarbonylethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.63 (chloroform:methanol:acetic acid=18:1:1): NMR (DMSO-d₆): δ7.92 (1H, d, J=7.2 Hz), 7.46-7.23 (5H, m), 5.88 (2H, s), 5.09 (2H, s),4.68-4.49 (1H, m), 3.60 (3H, s), 3.12 (2H, t, J=7.0 Hz), 2.93-2.51 (4H,m).

EXAMPLE 6(31)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methoxycarbonylethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.46 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.87-7.69 (1H, m), 7.48-7.24 (5H, m), 5.75 (2H, s), 5.09 (2H, s),4.64-4.45 (1H, m), 3.60 (3H, s), 3.05-2.56 (6H, m).

EXAMPLE 6(32)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrrol-2-ylmethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.50 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ13.10-11.90 (1H, br), 8.00 (1H, d-like, J=7.0 Hz), 7.50-7.21 (5H,m),6.68-6.60 (1H, m), 6.06-5.71 (4H, m), 5.09 (2H, s), 4.74-4.52 (1H, m),4.22 (2H, s), 3.53 (3H, s), 2.91-2.54 (2H, m).

EXAMPLE 6(33)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrrol-2-ylmethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.38 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ13.22-11.20 (1H, br), 8.06-7.92 (1H, m), 7.46-7.16 (6H, m), 6.87 (1H,brs), 6.28 (1H, brs), 5.06 (3H, brs), 4.51 (1H, d, J=17.0 Hz)z 4.20 (1H,d, J=117.0 Hz), 3.69 (3H, s), 2.74-2.46 (2H, m).

EXAMPLE 6(34)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-2-ylmethyl)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.29 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.71 (1H, d, J=4.4 Hz), 8.27-8.09 (1H, m), 8.03 (1H, d, J=7.8 Hz),7.77-7.55 (2H, m),.7.48-7.20 (5H, m), 5.98 (2H, s), 5.09 (2H, s), 4.64(3H,.brs), 2.83 (1H, dd, J=16.8 and 5.8 Hz), 2.64 (1H, dd, J=16.8 and6.8 Hz).

EXAMPLE 6(35)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-2-ylmethyl)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.14 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.64-8.52 (1H, m), 8.13 (1H, d, J=7.8 Hz), 8.00 (1H, td, J=7.8 and 1.8Hz), 7.65-7.44 (2H, m), 7.44-7.23 (5H, m), 5.90 (2H, s), 5.06 (2H, s),4.78-4.55 (1H, m), 4.47 (2H, s), 2.83 (1H, dd, J=17.0 and 6.0 Hz), 2.67(1H, dd, J=17.0 and 6.8 Hz).

EXAMPLE 6(36)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-3-ylmethyl)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.37 (chloroform:methanol:acetic acid=89:10:1); NMR (DMSO-d₆): δ8.76 (1H, brs), 8.72-8.61 (1H, m), 8.19-8.05 (1H, m), 8.05-7.96 (1H, m),7.78-7.64 (1H, m), 7.50-7.22 (5H, m), 5.95 (2H, s), 5.08 (2H, s),4.70-4.52 (1H, m), 4.45 (2H, s), 2.90-2.50 (2H, m).

EXAMPLE 6(37)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-3-ylmethyl)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.18 (chloroform:methanol:acetic acid=89:10:1); NMR (DMSO-d₆): δ8.70-8.52 (2H, m), 8.20-8.09 (1H, m), 7.92-7.78 (1H, m), 7.55-7.43 (1H,m), 7.43-7.21 (5H, m), 5.86 (2H, s), 5.10 (2H, s), 4.70-4.58 (1H, m),4.21 (2H, s), 2.95-2.60 (2H, m).

EXAMPLE 6(38)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-difluorophenylmethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.54 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.10-7.90 (1H, m), 7.63-7.03 (8H, m), 5.93 (2H, brs), 5.08 (2H, s),4.72-4.53 (1H, m), 4.27 (2H, s), 2.90-2.55 (2H, m).

EXAMPLE 6(39)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-difluorophenylmethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.36 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.07 (1H, brs), 7.60-7.08 (8H, m), 5.84 (2H, brs), 5.10 (2H, s),4.73-4.56 (1H, m), 4.13 (2H, s), 2.90-2.60(2H, m).

EXAMPLE 6(40)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(phenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.39 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 7.76 (1H, m),7.58-7.22 (10H, m), 6.00 (2H, brs), 5.06 (2H, s), 4.54 (1H, m), 2.62(2H, m).

EXAMPLE 6(41)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(phenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.33 (chloroform:methanol=4:1); NMR (DMSO-d6): δ 7.99 (1H, dr),7.60-7.23 (total 10H, m), 5.73 (2H, brs), 5.09 (2H, s), 4.60 (1H, m),2.71 (2H, m).

EXAMPLE 6(42)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.41 (chloroform:methanol=4 1); NMR (DMSO-d₆): δ 7.98 (1H, d,J=7.5 Hz), 7.69 and 7.68 (each 1H, each d, J=9.0, 7.5 Hz), 7.55 (1H, dd,J=9.0, 7.5 Hz), 7.44-7.24 (5H, m), 5.98 (2H, brs), 5.07 (2H, s), 4.61(1H, m), 2.80 and 2.62 (each 1H, each dd, J=16.5, 6.0 Hz).

EXAMPLE 6(43)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.32 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 7.78 (1H, m),7.67 and 7.66 (each 1H, each d, J=9.0, 7.0 Hz), 7.56 (1H, dd, J=9.0, 7.5Hz), 7.41-7.17 (5H, m), 5.80 (2H, br), 5.13 and 5.03 (each 1H, each d,J=12.0 Hz), 4.54 (1H, m), 2.63 (2H, m).

EXAMPLE 6(44)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethylphenylmethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=95:4:1); NMR (DMSO-d₆): δ12.47 (1H, brs), 8.02-7.88 (1H, m), 7.56-7.15 (5H, m), 7.10-6.80 (3H,m), 5.88 (2H, brs), 5.07 (2H, s), 4.70-4.47 (1H, m), 4.20 (2H, s),2.88-2.50 (2H, m), 2.33 (6H, s).

EXAMPLE 6(45)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethylphenylmethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.09 (chloroform:methanol:acetic acid=95:4:1); NMR (DMSO-d₆): δ8.05 (1H, d, J=8.0 Hz), 7.42-7.20 (5H, m), 7.16-6.92 (3H, m), 5.82 (2H,brs), 5.10 (2H, s), 4.72-4.55 (1H, m), 3.98 (2H, s) 2.90-2.63 (2H, m),2.12 (6H, s).

EXAMPLE 6(46)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(cyclohexylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.26 (chloroform:methanol:acetic acid=95:4:1); NMR (DMSO-d₆): δ12.50 (1H, brs), 7.94 (1H, brs), 7.60-7.10 (5H, m), 5.88 (2H, brs), 5.09(2H, s), 4.70-4.51 (1H, m), 2.89-2.47 (4H, m), 1.82-1.40 (6H, m),1.35-0.74 (5H, m).

EXAMPLE 6(47)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(cyclohexylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.11 (chloroform:methanol:acetic acid=95:4:1); NMR (DMSO-d₆): δ8.04 (1H, d, J=7.4 Hz), 7.41-7.23 (5H, m), 5.67 (2H, brs), 5.09 (2H, s),4.67-4.50 (1H, m), 2.88-2.60 (2H, m), 2.58 (2H, d, J=6.6 Hz) 1.82-1.41(6H, m), 1.36-0.78 (5H, m).

EXAMPLE 6(48)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methylphenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=95:4:1); NMR (DMSO-d₆): δ7.95 (1H, brs), 7.60-7.10 (9H, m), 5. 93 (2H, brs), 5.08 (2H, s),4.73-4.51 (1H, m), 2.83-2.54 (2H, m), 2.31 (3H, s).

EXAMPLE 6(49)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methylphenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.14 (chloroform:methanol:acetic acid=95:4:1); NMR (DMSO-d₆): δ8.10-7.93 (1H, brs), 7.47-7.16 (9H, m), 5.72 (2H, brs), 5.11 (2H, s),4.73-4.55 (1H, m), 2.90-2.59 (2H, m), 2.32 (3H, s).

EXAMPLE 6(50)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.26 (chloroform:methanol:acetic acid=95:4:1); NMR (DMSO-d₆): δ12.50 (1H, brs), 8.01 (1H, d, J=7.4 Hz), 7.60-7.42 (4H, m), 7.42-7.23(5H, m), 6.03 (2H, s), 5.09 (2H, s), 4.78-4.48 (1H, m), 2.90-2.57 (2H,m).

EXAMPLE 6(51)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.22 (chloroform:methanol:acetic acid=95:4:1); NMR (DMSO-d₆): δ12.47 (1H, brs), 8.15-7.96 (1H, m), 7.70-7.41 (4H, m), 7.41-7.23 (5H,m), 5.77 (2H, s), 5.10 (2H, s), 4.75-4.52 (1H, m), 2.90-2.55 (2H, m).

EXAMPLE 6(52)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-4-yl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.35 (chloroform:methanol:acetic acid=10:1:1); NMR (DMSO-d₆): δ13.36-11.90 (1H, br), 8.81 (2H, d, J=5.3 Hz), 8.08 (1H, d, J=7.5 Hz),7.82 (2H, d, J=5.3 Hz), 7.52-7.14 (5H, m), 6.00 (2H, s), 5.09 (2H, s),4.80-4.45 (3H, m), 2.97-2.57 (2H, m).

EXAMPLE 6(53)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-4-yl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.11 (chloroform:methanol:acetic acid=10:1:1); NMR (DMSO-d₆): δ8.85 (2H, d, J=6.4 Hz), 8.17 (1H, d, J=7.4 Hz), 7.88 (2H, d, J=6.4 Hz),7.52-7.09 (5H, m), 6.06-5.74 (2H, m), 5.11 (2H, s), 4.73-4.56 (1H, m),4.51 (2H, s), 2.92-2.59 (2H, m).

EXAMPLE 6(54)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3,5-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.40 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 8.01 (1H, m),7.64 (1H, d, J=1.5 Hz), 7.52 (2H, d, J=1.5 Hz), 7.37 (5H, m), 6.08 (2H,br), 5.08 (2H, s), 4.64 (1H, m), 2.89-2.56 (2H, m).

EXAMPLE 6(55)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3,5-dichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.30 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 8.06 (1H, m),7.69 (1H, d, J=1.5 Hz), 7.58 (2H, brs), 7.36 (5H, m), 5.82 (2H, br),5.10 (2H, s), 4.64 (1H, m), 2.75 (2H, m).

EXAMPLE 6(56)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrimidin-2,4-dion-3-ylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.36 (chloroform:methanol:acetic acid=20:2:1); NMR (DMSO-d₆): δ7.82 (1H, d, J=8 Hz), 7.76 (1H, d, J=8 Hz), 7.38 (5H, m), 5.92 (2H, br),5.75 (1H, d, J=8 Hz), 5.22 (2H, s), 5.08 (2H, s), 4.58 (1H, q, J=8 Hz),3.28 (3H, s), 2.82-2.50 (2H, m).

EXAMPLE 6(57)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrimidin-2,4-dion-3-ylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.18 (chloroform:methanol:acetic acid=20:2:1); NMR (DMSO-d₆): δ7.78 (1H, d, J=8 Hz), 7.60 (1H, d, J=8 Hz), 7.36 (5H, m), 6.00 (1H, d,J=17 Hz), 5.88 (1H, d, J=17 Hz), 5.56 (1H, d, J=8 Hz), 5.20-4.96 (4H,m), 4.46 (1H, J=8 Hz), 3.30 (3H, s), 2.80-2.55 (2H, m).

EXAMPLE 6(58)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloroethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.52 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ7.84-7.61 (1H, m), 7.52-7.16 (5H, m), 6.07-5.80 (2H, m), 5.08 (2H, s),4.63-4.42 (1H, m), 3.99 (2H, t, J=6.6 Hz), 3.35 (2H, t, J=6.6 Hz), 2.62(2H, d-like, J=5.6 Hz).

EXAMPLE 6(59)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloroethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.22 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.06-7.86 (1H, m), 7.56-7.20 (5H, m), 5.76 (2H, brs), 5.10 (2H, s),4.68-4.49 (1H, m), 3.94 (2H, t, J=6.8 Hz), 3.25 (2H, t, J=6.8 Hz), (2H,t, J=2.85-2.60 (2H, m).

EXAMPLE 6(60)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(phenylcarbonyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.37 (chloroform ethanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.21 (2H, d, J=7.0 Hz), 7.84-7.56 (4H, m), 7.35 (5H, m), 6.21 (2H, br),5.08 (2H, s), 4.58 (1H, m), 2.64 (2H, br).

EXAMPLE 6(61)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(phenylcarbonyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.45 (chloroform:ethanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.25 (2H, d, J=7.0 Hz), 8.00-7.58 (4H, m), 7.48-7.20 (5H, m), 6.09-5.81(2H, m), 5.10 (2H, s), 4.65 (1H, m), 2.66 (2H, m).

EXAMPLE 6(62)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-6-fluorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=45:4:1); NMR (DMSO-d₆): δ12.45 (1H, brs), 8.02-7.78 (1H, m), 7.50-7.20 (8H, m), 5.90 (2H, s),5.07 (2H, s), 4.70-4.50 (1H, m), 4.36 (2H, s), 2.90-2.53 (2H, m).

EXAMPLE 6(63)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-6-fluorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.39 (chloroform:methanol:acetic acid=45:4:1); NMR (DMSO-d₆): δ12.40 (1H, brs), 8.13-7.99 (1H, m), 7.50-7.15 (8H, m), 5.85 (2H, s),5.10 (2H, s), 4.74-4.56 (1H, m), 4.19 (2H, s), 2.90-2.60 (2H, m).

EXAMPLE 6(64)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(cyclohexylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.63 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.50 (1H, brs), 8.05-7.90 (1H, m), 7.63-7.42 (5H, m), 5.95 (2H, s),5.09 (2H, s), 4.70-4.57 (1H, m), 3.63-3.45 (1H, m), 2.90-2.60 (2H, m),2.10-1.10 (10H, m).

EXAMPLE 6(65)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(cyclohexylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.54 (chloroform:methanol:acetic acid=18:1:1); NMR(DMSO-d₆): δ12.43 (1H, brs), 8.07-7.91 (1H, m), 7.42-7.21 (5H, m), 5.60 (2H, s),5.10 (2H, s), 4.70-4.51 (1H, m), 3.70-3.52 (1H, m), 2.89-2.53 (2H, m),2.10-1.11 (10H, m).

EXAMPLE 6(66)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methoxyphenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.55 (chloroform:methanol:acetic acid=45:4:1); NMR (DMSO-d₆): δ12.49 (1H, brs), 8.04-7.83 (1H, m), 7.52 (2H, d, J=8.5 Hz), 7.45-7.22(5H, m), 7.00 (2H, d, J=8.5 Hz), 5.94 (2H, s), 5.07 (2H, s), 4.70-4.50(1H, m), 3.78 (3H, s), 2.90-2.53 (2H, m).

EXAMPLE 6(67)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-methoxyphenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=45:4:1); NMR (DMSO-d₆): δ8.08-7.97 (1H, m), 7.51 (2H, d, J=8.9 Hz), 7.42-7.25 (5H, m), 6.92 (2H,d, J=8.5 Hz), 5.69 (2H, s), 5.11 (2H, s), 4.71-4.53 (1H, m), 3.78 (3H,s), 2.90-2.53 (2H, m).

EXAMPLE 6(68)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.53 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ12.52 (1H, brs), 8.02 (1H, d, J=8 Hz), 7.70-7.52 (1H, m), 7.52-7.20 (8H,m), 6.06 (2H, s), 5.09 (2H, s), 4.78-4.49 (1H, m), 2.83 (1H, dd, J=17and 6 Hz), 2.65 (1H, dd, J=17 and 7 Hz).

EXAMPLE 6(69)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.07-7.79 (1H, m), 7.75-7.12 (9H, m), 5.78 (2H, brs), 5.08 (2H, s),4.71-4.41 (1H, m), 2.87-2.55 (2H, m).

EXAMPLE 6(70)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.57 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.85-12.15 (1H, br), 8.10 (1H, d, J=7 Hz), 7.82 (1H, d, J=7 Hz),7.58-7.20 (7H, m), 6.05 (2H, s), 5.09 (2H, s), 4.82-4.46 (1H, m), 2.82(1H, dd, J=17 and 6 Hz), 2.65 (1H, dd, J=17 and 7 Hz).

EXAMPLE 6(71)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-dichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.53 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.03 (1H, d, J=7 Hz), 7.82 (1H, s-like), 7.66-7.12 (7H, m), 5.76 (2H,brs), 5.09 (2H, s), 4.78-4.44 (1H, m), 2.95-2.53 (2H, m).

EXAMPLE 6(72)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-6-methylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.56 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.5 (1H, brs), 7.96 (1H, d, J=7.6 Hz), 7.51-7.28 (8H, m), 5.95 (2H,brs), 5.08 (2H, s), 4.67-4.56 (1H, m), 2.80 (1H, dd, J=5.4, 17 Hz), 2.63(1H, dd, J=7.0, 17 Hz), 2.47 (3H, s).

EXAMPLE 6(73)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-6-methylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.5 (1H, brs), 8.08 (1H, d, J=9.6 Hz), 7.51-7.23 (8H, m), 5.75 (2H,brs), 5.12 (2H, s), 4.71-4.61 (1H, m), 2.92-2.67 (2H, m), (3H, s).

EXAMPLE 6(74)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethylphenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.40 (chloroform:methanol:acetic acid=40:1:1); NMR (DMSO-d₆): δ7.99 (d, J=8.0 Hz, 1H), 7.76 (d, J=8.6 Hz, 2H), 7.62 (d, J=8.6 Hz, 2H),7.4-7.2 (m, 5H), 6.07 (s, 2H), 5.09 (s, 2H), 4.8-4.6 (m, 1H), 2.78 (dd,J=6.0, 17.0 Hz, 1H), 2.65 (dd, J=7.0,17.0 Hz, 1H).

EXAMPLE 6(75)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethylphenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.45 (chloroform:methanol:acetic acid=40:1:1); NMR (DMSO-d₆): δ8.0-7.9 (m, 1H), 7.78 (d, J=8.5 Hz, 2H), 7.67 (d, J=8.5 Hz, 2H), 7.4-7.3(m, 5H), 5.79 (s, 2H), 5.09 (s, 2H), 4.7-4.5 (m, 2.8-2.6 (m, 2H).

EXAMPLE 6(76)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(naphthalen-2-ylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ12.50 (1H, brs), 8.12 (1H, s), 8.00-7.86 (4H, m), 7.62-7.45 (3H, m),7.43-7.20 (5H, m), 5.99 (2H, s), 5.07 (2H, s), 4.73-4.53 (1H, m),2.90-2.55 (2H, m).

EXAMPLE 6(77)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(naphthalen-2-ylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.31 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ12.57 (1H, brs), 8.15 (1H, s), 8.10-7.87 (4H, m), 7.69-7.44 (3H, m),7.42-7.23 (5H, m), 5.78 (2H, s), 5.10 (2H, s), 4.73-4.55 (1H, m),2.90-2.55 (2H, m).

EXAMPLE 6(78)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ12.48 (1H, brs), 7.96 (1H, brs), 7.60-7.40 (9H, m), 5.98 (2H, brs), 5.06(2H, s), 4.70-4.50 (1H, m), 2.88-2.53 (2H, m), 1.26 (9H, s).

EXAMPLE 6(79)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ8.10-7.90 (1H, m), 7.60-7.25 (9H, m), 5.70 (2H, brs), 5.09 (2H, s),4.70-4.53 (1H, m), 2.90-2.53 (2H, m), 1.27 (9H, s).

EXAMPLE 6(80)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethyloxyphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=30:1:1); NMR (DMSO-d₆): δ8.1-8.0 (m, 1H), 7.66 (d, J=8.8 Hz, 2H), 7.43 (d, J=8.8 Hz, 2H), 7.5-7.3(m, 5H), 5;76 (brs, 2H), 5.10 (s, 2H), 4.7-4.6 (m, 1H, )2.9-2.6 (m, 2H).

EXAMPLE 6(81)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethyloxyphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ8.1-7.9 (m, 1H), 7.63 (d, J=8.8 Hz, 2H), 7.43 (d, J=8.8 Hz, 2H), 7.5-7.2(m, 5H), 6.2-5.9 (m, 2H), 5.09 (s, 2H), 4.7-4.5 (m, 1H), 2.9-2.6 (m,2H).

EXAMPLE 6(82)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.61 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ11.9 (1H, brs), 7.96 (1H, d, J=7.8 Hz), 7.84 (1H, d, J=8.8 Hz), 7.71(1H, d, J=8.8 Hz), 7.39-7.30 (5H, m), 5.97 (2H, brs), 5.09 (2H, s),4.68-4.58 (1H, m), 2.80 (1H, dd, J=5.6, 16.6 Hz), 2.64 (1H, dd, J=7.0,16.6 Hz).

EXAMPLE 6(83)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.48 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.08 (1H, d, J=7.4 Hz), 7.86 (1H, d, J=8.8 Hz), 7.71 (1H, d, J=8.8 Hz),7.42-7.26 (5H, m), 5.78 (2H, brs), 5.12 (2H, s), 4.75-4.60 (1H, m),2.93-2.70 (2H, m).

EXAMPLE 6(84)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-dimethylphenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.38 (chloroform:methanol:acetic acid=94:3:3); NMR (DMSO-d₆): δ8.02-7.89 (1H, m), 7.43-7.22 (6H, m), 7.19 (1H, s), 7.06 (1H, d, J=8.0Hz), 5.92 (2H, brs), 5.07 (2H, s), 4.70-4.50 (1H, m), 2.90-2.53 (2H, m),2.32 (3H, s), 2.29 (3H, s).

EXAMPLE 6(85)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-dimethylphenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.29 (chloroform:methanol:acetic acid=94:3:3); NMR (DMSO-d₆): δ8.10-7.96 (1H, m), 7.43-7.25 (6H, m), 7.20 (1H, s), 7.07 (1H, d, J=7.4Hz), 5.69 (2H, brs), 5.10 (2H, s), 4.70-4.53 (1H, m), 2.90-2.53 (2H, m),2.30 (6H, s).

EXAMPLE 6(86)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,5-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.48 (chloroform:methanol:acetic acid=96:3:1); NMR (DMSO-d₆): δ8.08-7.90 (1H, m), 7.65 (1H, dd, J=8.7, 2.9 Hz), 7.48 (1H, d, J=8.7 Hz),7.42-7.23 (6H, m), 6.05 (2H, brs), 5.09 (2H, s), 4.70-4.52 (1H, m),2.90-2.55 (2H, m).

EXAMPLE 6(87)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,5-dichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.40 (chloroform:methanol:acetic acid=96:3:1); NMR (DMSO-d₆): δ8.05 (1H, brs), 7.70-7.58 (1H, m), 7.55-7.45 (2H, m), 7.45-7.21 (5H, m),5.83 (2H, brs), 5.09 (2H, s), 4.75-4.55 (1H, m), 2.90-2.55 (2H, m).

EXAMPLE 6(88) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-bromophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=30:1:1); NMR (DMSO-d₆): δ12.53 (brs, 1H), 8.00 (d, J=8.0 Hz, 1H), 7.62 (d, J=8.6 Hz, 2H), 7.46(d, J=8.6 Hz, 2H), 7.5-7.3 (s, 4H), 6.03 (s, 2H), 5.09 (s, 2H), 4.8-4.6(m, 1H), 3.0-2.6 (m, 2H).

EXAMPLE 6(89) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-bromophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.26 (chloroform:methanol:acetic acid=30:1:1); NMR (DMSO-d₆): δ12.57 (brs, 1H), 8.07 (d, J=7.4 Hz, ₁H), 7.63 (d, J=8.6 Hz, 2H), 7.46(d, J=8.6 Hz, 2H), 7.5-7.2 (m, 4H), 5.79 (s, 2H), 5.11 (s, 2H), 4.8-4.6(m, 1H), 3.0-2.6 (m, 2H).

EXAMPLE 6(90)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.60 (chloroform:methanol:acetic acid=96:3:1); NMR (DMSO-d₆): δ7.95 (1H, d, J=7.6 Hz), 7.53 (2H, s), 7;40-7.25 (5H, m), 5.96 (2H, s),5.08 (2H, s), 4.70-4.50 (1H, m), 2.79 (1H, dd, J=16.8, 6.0 Hz), 2.61(1H, dd, J=16.8, 6.8 Hz), 2.36 (3H, s).

EXAMPLE 6(91)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.50 (chloroform:methanol:acetic acid=96:3:1); NMR (DMSO-d₆): δ8.04 (1H, brs), 7.52 (2H, s), 7.45-7.20 (5H, m), 5.74 (2H, s), 5.11 (2H,s), 4.76-4.56 (1H, m), 2.90-2.65 (2H, m), 2.36 (3H, s).

EXAMPLE 6(92)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3,4-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.48 (chloroform:methanol:acetic acid=36:1:1); NMR (CDCl₃): δ7.99 (1H, d, J=7.6 Hz), 7.75 (1H, d, J=2.2 Hz), 7.67 (1H, d, J=8.6 Hz),7.46 (1H, dd, J=2.2, 8.6 Hz), 7.40-7.30 (5H, m), 6.00 (2H, brs), 5.09(2H, s), 4.69-4.59 (1H, m), 2.87-2.61 (2H, m).

EXAMPLE 6(93)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3,4-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=36:1:1); NMR (CDCl₃): δ8.06 (1H, d, J=7.4 Hz), 7.80 (1H, d, J=2.2 Hz), 7.68 (1H, d, J=8.6 Hz),7.50 (1H, dd, J=2.2, 8.6 Hz), 7.40-7.29 (5H, m), 5.77 (2H, br s), 5.11(2H, s), 4.69-4.59 (1H, m), 2.88-2.64 (2H, m).

EXAMPLE 6(94) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-bromotetrazol-2-yl)pentanoic acid

TLC:Rf 0.51 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆):δ7.93(1H, d, J=7.4 Hz), 7.56-7.13 (5H, m), 6.01 (2H, brs), 5.09 (2H, s),4.73-4.49 (1H, m), 2.92-2.52 (2H, m).

EXAMPLE 6(95)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-nitrophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.53 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.80-10.36 (1H, br), 8.22 (2H, d, J=9.0 Hz), 8.00 (1H, d, J=7.8 Hz),7.61 (2H, d, J=9.0 Hz), 7.47-7.18 (5H, m), 6.05 (2H, brs), 5.09 (2H, s),4.80-4.52 (1H, m), 2.93-2.56 (2H, m).

EXAMPLE 6(96)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-nitrophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.37 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.22 (2H, d, J=9.0 Hz), 7.98 (1H, d, J=7.8 Hz), 7.66 (2H, d, J=9.0 Hz),7.46-7.19 (5H, m), 5.79 (2H, brs), 5.09 (2H, s), 4.74-4.46 (1H, m),2.87-2.54 (2H, m).

EXAMPLE 6(97)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(naphthalen-1-ylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.47 (chloroform:methanol:acetic acid=96:3:1); NMR (DMSO-d₆): δ12.43 (1H, brs), 8.26 (1H, d, J=8.6 Hz), 8.16-7.80 (4H, m), 7.74-7.47(3H, m), 7.42-7.22 (5H, m), 5.94 (2H, s), 5.06 (2H, s), 4.75-4.50 (1H,m), 2.87-2.52 (2H, m).

EXAMPLE 6(98)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(naphthalen-1-ylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.37 (chloroform:methanol:acetic acid=96:3:1); NMR (DMSO-d₆): δ12.56 (1H, brs), 8.32-7.97 (4H, m), 7.93 (1H, d, J=7.0 Hz), 7.70-7.49(3H, m) 7.41-7.10 (5H, m), 5.86 (2H, brs), 5.12 (2H, s ), 4.78-4.58 (1H,m), 2.94-2.62 (2H, m).

EXAMPLE 6(99)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-di-t-butylphenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.26 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.60 (1H, d, J=7 Hz), 7.46 (1H, d, J=2 Hz), 7.37-7.19 (7H, m), 5.97 (2H,dd, J=17 and 24 Hz), 5.04 (2H, s), 4.48 (1H, m), 2.65-2.52 (2H, m), 1.49and 1.27 (each 9H, each s).

EXAMPLE 6(100)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4-di-t-butylphenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.79 (1H, d, J=8 Hz), 7.48 (1H, s), 7.35-7.18 (7H, m), 5.77 (2H, brs),5.06 (2H, s), 4.52 (1H, m), 2.61 (2H, d-like), 1.46 and 1.29 (each 9H,each s).

EXAMPLE 6(101)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imidazol-1-ylmethyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.44 (chloroform:methanol:acetic acid=10:5:1); NMR (DMSO-d₆): δ9.28 (1H, s), 8.02 (1H, d, J=7.0 Hz), 7.80 (1H, s), 7.71 (1H, s),7.42-7.30 (5H, m), 6.04 (2H, s), 5.91 (2H, s), 5.09 (2H, s), 4.62 (1H,m), 2.90-2.58 (2H, m).

EXAMPLE 6(102)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imidazol-1-ylmethyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.38 (chloroform:methanol:acetic acid=10:5:1); NMR (DMSO-d₆): δ9.22 (1H, s), 8.20 (1H, d, J=7.0 Hz), 7.72 (1H, s), 7.68 (1H, s),7.40-7.26 (5H, m), 6.10-5.88 (2H, m), 5.81 (2H, s), 5.12 (2H, s), 4.72(1H, m), 2.92-2.62 (2H, m).

EXAMPLE 6(103)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methoxyphenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.34 (chloroform:methanol:acetic acid=36:1:1); NMR (DMSO-d₆): δ7.98 (1H, d, J=7.6 Hz), 7.42-7.30 (6H, m), 7.25(1H, d, J=7.4 Hz), 7.10(1H, d, J=7.4 Hz), 7.00-6.92 (1H, m), 5.97 (2H, brs), 5.09 (2H, s),4.68-4.58 (1H, m), 3.80 (3H, s), 2.87-2.60 (2H, m).

EXAMPLE 6(104)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methoxyphenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.29 (chloroform:methanol:acetic acid=36:1:1); NMR (DMSO-d₆): δ8.03 (1H, d, J=6.8 Hz), 7.46-7.31 (7H, m), 7.09(1H, d, J=7.8 Hz),7.03-6.95 (1H, m), 5.72 (2H, brs), 5.10(2H, s), 4.68-4.58 (1H, m), 3.75(3H, s), 2.87-2.62 (2H, m).

EXAMPLE 6(105)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.38 (chloroform:methanol:water=50:10:1); NMR (DMSO-d₆): δ 7.97(1H, d, J=7.8 Hz), 7.40-7.26 (5H, m), 6.88 (2H, s), 5.95 (2H, brs), 5.08(2H, s), 4.60 (1H, m), 2.77 (6H, s), 2.84-2.72 (2H, m).

EXAMPLE 6(106)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.29 (chloroform:methanol:water=50:10:1); NMR (DMSO-d₆): δ 8.02(1H, m), 7.40-7.24 (5H, m), 6.87 (2H, s), 5.73 (2H, brs), 5.11 (2H, s),4.62 (1H, m), 3.00 (6H, s), 2.92-2.62 (2H, m).

EXAMPLE 6(107)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiophen-2-yl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.46 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.61(1H, d, J=8 Hz), 7.40-7.32 (6H, m), 6.96-6.94 (2H, m), 5.96 (2H, brs),5.07 (2H, s), 4.57-4.47 (1H, m), 4.46 (2H, s), 2.60 (2H, d-like).

EXAMPLE 6(108)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiophen-2-yl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.34 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.08(1H, d, J=8 Hz), 7.43-7.37 (6H, m), 6.97-6.94 (2H, m), 5.77 (2H, s),5.10 (2H, s), 4.64 (1H, m), 4.38 (2H, s), 2.76 (2H, m).

EXAMPLE 6(109)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-3-yl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.49 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.97(1H, d, J=7 Hz), 7.48 (1H, dd, J=3 and 5 Hz), 7.37-7.33 (5H, m),7.28-7.26 (1H, m), 7.02 (1H, d, J=5 Hz), 5.90 (2H, brs), 5.09 (2H, s),4.67-4.57 (1H, m), 4.25 (2H, s), 2.81 and 2. 64 (each 1H, each dd, J=7and 17 Hz).

EXAMPLE 6(110)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-3-yl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.37 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.06(1H, d, J=7 Hz), 7.48 (1H, dd, J=3 and 5 Hz), 7.40-7.31 (6H, m), 6.98(1H, d, J=5 Hz), 5.72 (2H, brs), 5.10 (2H, s), 4.67-4.58 (1H, m), 4.14(2H, s), 2.81 and 2.69 (each 1H, each dd, J=7 and 17 Hz).

EXAMPLE 6(111)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-imidazol-1-ylpropyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.50 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ7.97 (1H, d, J=7.8 Hz), 7.62 (1H, brs), 7.40-7.30 (5H, m), 7.19 (1H,brs), 6.92 (1H, brs), 5.87 (2H, s), 5.09 (2H, s), 4.61 (1H, m), 4.04(2H, t, J=7.0 Hz), 2.88-2.58 (4H, m), 2.14 (2H, m).

EXAMPLE 6(112)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-imidazol-1-ylpropyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.38 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ8.04 (1H, d, J=7.8 Hz), 7.62 (1H, brs), 7.40-7.30 (5H, m), 7.17 (1H, s),6.89 (1H, s), 5.69 (2H, s), 5.10 (2H, s), 4.60 (1H, m), 4.10-3.98 (2H,m), 2.90-2.62 (4H, m), 2.10 (2H, m).

EXAMPLE 6(113)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,3-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.19 (chloroform:methanol:acetic acid=36:1:1); NMR (DMSO-d₆): δ7.99 (1H, d, J=7.4 Hz), 7.64 (1H, d, J=8.0 Hz), 7.40-7.31 (6H, m), 7.24(1H, d, J=8.0 Hz), 6.05 (2H, brs), 5.10 (2H, s), 4.70-4.60 (1H, m),2.89-2.62 (2H, m).

EXAMPLE 6(114)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,3-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.16 (chloroform:methanol:acetic acid=36:1:1); NMR (DMSO-d₆): δ8.05 (1H, d, J=7.6 Hz), 7.71-7.66 (1H, m), 7.41-7.18 (7H, m), 5.81 (2H,brs), 5.09 (2H, s), 4.69-4.59 (1H, m), 2.88-2.63 (2H, m).

EXAMPLE 6(115)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethylphenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.48 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ12.40 (1H, brs), 7.92 (1H, d, J=8.8 Hz), 7.40-7.05 (8H, m) 5.90 (2H,brs), 5.05 (2H, s), 4.70-4.50 (1H, m), 2.84-2.50 (2H, m), 2.40 (6H, s).

EXAMPLE 6(116)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethylphenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.41 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ8.04 (1H, d, J=8.6 Hz), 7.42-7.10 (8H, m) 5.70 (2H, brs), 5.11 (2H, s),4.70-4.52 (1H, m), 2.91-2.60 (2H, m), 2.35 (6H, s).

EXAMPLE 6(117)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.25 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ7.98 (1H, d, J=8.0 Hz), 7.56 (1H, d, J=1.6 Hz), 7.43-7.20 (7H, m) 6.02(2H, brs), 5.07 (2H, s), 4.70-4.55 (1H, m), 2.80 (1H, dd, J=16.6, 5.7Hz), 2.62 (1H, dd, J=16.6, 6.6 Hz), 1.26 (9H, s).

EXAMPLE 6(118)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.19 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ8.10-7.95 (1H, m), 7.58 (1H, d, J=1.4 Hz), 7.53-7.21 (7H, m) 5.76 (2H,brs), 5.10 (2H, s), 4.70-4.54 (1H, m), 2.90-2.60 (2H, m), 1.29 (9H, s).

EXAMPLE 6(119)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,2,6,6-tetramethylpiperidin-2-ylmethyl)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.45 (chloroform:methanol:acetic acid=10:2:1); NMR (DMSO-d₆): δ9.32 (1H, brs), 8.08 (1H, d, J=7.6 Hz), 7.40-7.30 (5H, m), 6.07 (2H, s),5.10 (2H, s), 4.80-4.58 (3H, m), 2.92-2.58 (2H, m), 2.10-1.40 (18H, m).

EXAMPLE 6(120)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,2,6,6-tetramethylpiperidin-1-ylmethyl)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.66 (chloroform:methanol:acetic acid=10:2:1); NMR (DMSO-d₆): δ8.36 (1H, d, J=7.4 Hz), 7.40-7.24 (5H, m), 6.20-5.90 (2H, m), 5.11 (2H,s), 4.80-4.60 (3H, m), 2.96-2.60 (2H, m), 2.00-1.20 (18H, m).

EXAMPLE 6(121)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(N-phenyl-N-methylamino)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.25 (chloroform:methanol:water=90:10:1); NMR (DMSO-d₆): δ 7.96(1H, d, J=8 Hz), 7.48-7.32 (9H, m), 7.08 (1H, t, J=7 Hz), 5.81 (2H, s),5.09 (2H, s), 4.67-4.57 (1H, m), 3.49 (3H, s), 2.82 and 2.62 (each 1H,each dd, J=7 and 17 Hz).

EXAMPLE 6(122)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(N-phenyl-N-methylamino)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.19 (chloroform:methanol:acetic acid=90:10:1); NMR(DMSO-d₆): δ7.79 (1H, d, J=8 Hz), 7.42-7.28 (7H, m), 7.17-7.09 (1H, m), 6.96 (2H, d,J=8 Hz), 5.06 (2H, q-like), 5.01 (2H, s), 4.26-4.16 (1H, m), 3.30 (3H,s), 2.64-2.37 (2H, m).

EXAMPLE 6(123)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-diisopropylphenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.24 (chloroform:methanol:water=90:10:1); NMR (DMSO-d₆): δ 7.90(1H, d, J=8 Hz), 7.51-7.27 (8H, m), 5.87 (2H, brs), 5.07 (2H, s),4.62-4.52 (1H, m), 3.75-3.62 (2H, m), 2.97-2.62 (2H, m), 1.13 (12H, d,J=7 Hz).

EXAMPLE 6(124)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-diisopropylphenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.21 (chloroform:methanol:water=90:10:1); NMR (DMSO-d₆): δ 8.06(1H, d, J=7 Hz), 7.55-7.28 (8H, m), 5.73 (2H, brs), 5.11 (2H, s),4.71-4.61 (1H, m), 3.60-3.42 (2H, m), 3.04-2.66 (2H, m), 1.11 (12H, d,J=7 Hz).

EXAMPLE 6(125)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methyl-4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ12.47 (1H, brs), 7.98 (1H, J=7.6 Hz), 7.60-7.10 (8H, m) 5.98 (2H, s),5.08 (2H, s), 4.70-4.50 (1H, m), 2.81 (1H, dd, J=16.8, 5.8 Hz), 2.62(1H, dd, J=16.8, 6.8 Hz), 2.36 (3H, s), 1.28 (9H, s).

EXAMPLE 6(126)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-methyl-4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.32 (chloroform:methanol:acetic acid=46:3:1); NMR (DMSO-d₆): δ12.57 (1H, brs), 8.08 (1H, d, J=7.4 Hz), 7.60-7.10 (8H, m) 5.75 (2H, s),5.11 (2H, s), 4.70-4.55 (1H, m), 2.86 (1H, dd, J=17.6, 5.8 Hz), 2.68(1H, dd, J=17.6, 7.0 Hz), 2.35 (3H, s), 1.28 (9H, s).

EXAMPLE 6(127)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.48 (chloroform:methanol:acetic acid=47:2:1); NMR (DMSO-d₆): δ12.48 (1H, brs), 7.94 (1H, d, J=7.6 Hz), 7.35 (5H, brs), 7.24 (2H, s),5.92 (2H, s), 5.07 (2H, s), 4.70-4.50 (1H, m), 2.90-2.50 (2H, m), 2.41(6H, s), 1.28 (9H, s).

EXAMPLE 6(128)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=47:2:1); NMR (DMSO-d₆): δ12.50 (1H, brs), 8.11-7.90 (1H, m), 7.46-7.20 (5H, m), 7.25 (2H, s),5.71 (2H, s), 5.11 (2H, s), 4.72-4.53 (1H, m), 2.93-2.57 (2H, m), 2.35(6H, s), 1.29 (9H, s).

EXAMPLE 6(129)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.39 (chloroform:methanol:water=50:10:1); NMR (DMSO-d₆): δ 7.99(1H, d, J=7.8 Hz), 7.40-7.30 (5H, m), 6.79 (2H, s), 5.92 (2H, s), 5.07(2H, s), 4.60 (1H, m), 2.96 (6H, s), 2.88-2.54 (2H, m), 2.38 (6H, s).

EXAMPLE 6(130)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.36 (chloroform:methanol:water=50:10:1); NMR (DMSO-d₆): δ 8.10(1H, d, J=7.8 Hz), 7.40-7.26 (5H, m), 6.74 (2H, S), 5.69 (2H, s), 5.11(2H, s), 4.62 (1H, m), 2.97 (6H, s), 2.92-2.62 (2H, m), 2.30 (6H, s).

EXAMPLE 6(131)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzoimizazol-2-ylmethyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.30 (chloroform:methanol:acetic acid=20:1:1): NMR (DMSO-d₆): δ8.28-8.01 (1H, m), 7.62 (2H, dd, J=5.8 and 3.0 Hz), 7.50-7.28 (7H, m),5.97 (2H, brs), 5.02 (2H, s), 4.67 (3H, brs), 2.92-2.54 (2H, m).

EXAMPLE 6(132)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzoimizazol-2-ylmethyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.20 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.04 (1H, d, J=7.6 Hz), 7.79 (2H, dd, J=6.0 and 3.2 Hz), 7.51 (2H, dd,J=6.0 and 3.2 Hz), 7.42-7.20 (5H, m), 6.04 (2H, s), 5.08 (2H, s), 4.95(2H, s), 4.77-4.99 (1H, m), 2.84 (1H, dd, J=16.8 and 6.4 Hz), 2.65 (1H,dd, J=16.8 and 6.8 Hz).

EXAMPLE 6(133)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-isopropylphenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.34 (chloroform:methanol:acetic acid=36:1:1); NMR (DMSO-d₆): δ7.99 (1H, d, J=6.4 Hz), 7.47-7.25 (9H, m), 5.99 (2H, brs), 5.09 (2H, s),4.69-4.58 (1H, m), 2.98-2.60 (3H, m), 1.20 (6H, d, J=6.8 Hz).

EXAMPLE 6(134)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-isopropylphenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.27 (chloroform:methanol:acetic acid=36:1:1); NMR (DMSO-d₆): δ8.05 (1H, d, J=7.0 Hz), 7.49-7.28 (9H, m), 5.72 (2H, brs), 5.12 (2H, s),4.69-4.59 (1H, m), 2.98-2.63 (3H, m), 1.21 (6H, d, J=6.8 Hz).

EXAMPLE 6(135)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzothiazol-2-ylmethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.15 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ13.80-11.40 (1H, br), 8.20-7.86 (3H, m), 7.62-7.22 (7H, m), 6.29-5.68(2H, brs), 5.09 (2H, s), 4.87 (2H, s), 4.78-4.46 (1H, m) 2.82 (1H, dd,J=17.0 and 6.5 Hz), 2.65 (1H, dd, J=17.0 and 7.0 Hz).

EXAMPLE 6(136)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzothiazol-2-ylmethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.10 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ13.50-11.40 (1H, br), 8.19-7.84 (3H, m), 7.70-7.18 (7H, m), 6.15-5.60(2H, brs), 5.03 (2H, s), 4.98-4.50 (3H, m), 2.90-2.57 (2H, m).

EXAMPLE 6(137)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-2-ylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.29 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.89(2H, m), 7.78 (1H, m), 7.36 (5H, s), 6.07 (2H, s), 5.08 (2H, s), 4.55(1H, m), 2.66 (2H, m).

EXAMPLE 6(138)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-2-ylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.89(2H, m), 7.73 (1H, m), 7.35 (5H, s), 5.87 (2H, s), 5.07 (2H, s), 4.53(1H, m), 2.61 (2H, m).

EXAMPLE 6(139)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4,6-trichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=48:1:1); NMR (DMSO-d₆): δ12.49 (1H, brs), 8.05-7.84 (3H, m), 7.45-7.20 (5H, m), 5.98 (2H, s),5.07 (2H, s), 4.70-4.50 (1H, m), 2.90-2.50 (2H, m).

EXAMPLE 6(140)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,4,6-trichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.17 (chloroform:methanol:acetic acid=48:1:1); NMR (DMSO-d₆): δ12.57 (1H, brs), 8.10-8.00 (1H, m), 7.93 (2H, s), 7.43-7.20 (5H, m),5.80 (2H, s), 5.10 (2H, s), 4.80-4.55 (1H, m), 2.93-2.65 (2H, m).

EXAMPLE 6(141)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-(1,1-dimethylpropyl)phenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.26 (chloroform:methanol:acetic acid=48:1:1); NMR (DMSO-d₆): δ12.50 (1H, brs), 7.96 (1H, d, J=8.5 Hz), 7.59 (2H, s), 7.35 (5H, s),5.98 (2H, s), 5.07 (2H, s), 4.70 4.52 (1H, m), 2.90-2.50 (2H, m), 1.63(2H, q, J=7.5 Hz), 1.25 (6H, s), 0.64 (3H, t, J=7.5 Hz).

EXAMPLE 6(142)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-(1,1-dimethylpropyl)phenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.17 (chloroform:methanol:acetic acid=48:1:1); NMR (DMSO-d₆): δ12.56 (1H, brs), 8.09 (1H, d, J=8.5 Hz), 7.59 (2H, s), 7.42-7.08 (5H,s), 5.80 (2H, s), 5.10 (2H, s), 4.75-4.60 (1H, m), 2.90-2.50 (2H, m),1.63 (2H, q, J=7.5 Hz), 1.25 (6H, s), 0.64 (3H, t, J=7.5 Hz).

EXAMPLE 6(143)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1,1-diphenylmethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.29 (chloroform:methanol:acetic acid=38:1:1); NMR (DMSO-d₆): δ7.94 (1H, d, J=7.0 Hz), 7.50-7.12 (15H, m), 5.93 (3H, m), 5.08 (2H, s),4.72-4.51 (1H, m), 2.92-2.53 (2H, m).

EXAMPLE 6(144)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1,1-diphenylmethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.16 (chloroform:methanol:acetic acid=38:1:1); NMR (DMSO-d₆): δ8.05 (1H, d, J=7.0 Hz,), 7.53-7.08 (15H, m), 5.92-5.57 (3H, m), 5.10(2H, s), 4.72-4.46 (1H, m), 2.94-2.55 (2H, m).

EXAMPLE 6(145)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-4-fluorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.16 (chloroform:methanol:acetic acid=38:1:1); NMR (DMSO-d₆): δ8.05 (1H, d, J=7.0Hz,), 7.53-7.08 (15H, m), 5.92-5.57 (3H, m), 5.10 (2H,s), 4.72-4.46 (1H, m), 2.94-2.55 (2H, m).

EXAMPLE 6(145)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-4-fluorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:acetic acid=38:1:1); NMR (DMSO-d₆): δ12.80-12.10 (1H, br), 7.99 (1H, d, J=8.0 Hz), 7.75-7.52 (2H, m),7.52-7.18 (6H, m), 6.02 (2H, brs), 5.09 (2H, s), 4.80-4.45 (1H, m),2.95-2.52 (2H, m).

EXAMPLE 6(146)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-chloro-4-fluorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.28 (chloroform:methanol:acetic acid=38:1:1); NMR (DMSO-d₆): δ8.02 (1H, d, J=7.0 Hz,), 7.82-7.54 (2H, m), 7.54-7.16 (6H, m), 5.76 (2H,brs), 5.10 (2H, s), 4.75-4.45 (1H, m), 2.92-2.55 (2H, m).

EXAMPLE 6(147)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(5-imidazol-1-ylpentyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.39 (chloroform:methanol:water=90:10:1); NMR (DMSO-d₆): δ 9.08(1H, s), 8.15 (1H, d, J=7.0 Hz),.7.75 (1H, s), 7.59 (1H, s), 7.80-6.90(5H, brs), 5.91 (2H, brs), 5.12 (2H, s), 4.88-4.51 (1H, m), 4.40-4.00(2H, m), 3.05-2.60 (4H, m), 2.08-1.47 (4H, m), 1.47-1.04 (2H, m).

EXAMPLE 6(148)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(5-imidazol-1-ylpentyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.13 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 9.21 (1H, s),8.14 (1H, d, J=7.0 Hz), 7.79 (1H, s), 7.67 (1H, s), 7.52-7.20 (5H, brs),5.74 (2H, brs), 5.10 (2H, s), 4.79-4.48 (1H, m), 4.33-4.03 (2H, m),3.00-2.56 (4H, m), 2.04-1.48 (4H, m), 1.48-1.08 (2H, m).

EXAMPLE 6(149)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-dimethylaminoethyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.29 (chloroform:methanol:water=24:8:1); NMR (DMSO-d₆): δ11.80-9.42 (1H, br), 8.26-8.05 (1H, m), 7.49-7.24 (5H, m), 5.98-5.70(2H, br), 5.11 (2H, s), 4.80-4.50 (1H, m), 3.55-3.05 (4H, m), 2.96-2.60(2H, m), 2.82 (6H, s).

EXAMPLE 6(150)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-dimethylaminoethyl)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.18 (chloroform:methanol:water=24:8:1); NMR (DMSO-d₆): δ13.30-11.65 (1H, br), 11.10-10.60 (1H, br), 8.05 (1H, d, J=8.0 Hz),7.55-7.20 (5H, m), 5.99 (2H, s), 5.10 (2H, s), 4.70-4.50 (1H, m),3.60-3.30 (4H, m), 2.96-2.55 (2H, m), 2.82 (6H, s).

EXAMPLE 6(151)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-fluorophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.28 (chloroform:methanol:acetic acid=38:1:1); NMR (DMSO-d₆): δ13.40-11.50 (1H, br), 8.04 (1H, s), 8.19-7.94 (3H, m), 7.48-7.14 (7H,m), 6.00 (2H, brs), 5.09 (2H, s), 4.77 (2H, s), 4.80-4.47 (1H, m),2.94-2.53 (2H, m).

EXAMPLE 6(152)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-fluorophenyl)thiazol-2-ylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.21 (chloroform:methanol:acetic acid=38:1:1); NMR (DMSO-d₆): δ8.07 (1H, s), 8.24-7.80 (3H, m), 7.46-7.15 (7H, m), 5.92 (2H, brs), 5.04(2H, s), 4 .84-4.51 (3H, m), 2.93-2.55 (2H, m).

EXAMPLE 6(153)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-chlorophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.20 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ13.10-11.30 (1H, br), 8.11 (1H, s), 8.12-7.80 (3H, m), 7.58-7.20 (7H,m), 6.01 (2H, brs), 5.09 (2H, s), 4.78 (2H, s), 4.77-4.46 (1H, m),2.92-2.53 (2H, m).

EXAMPLE 6(154)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-chlorophenyl)thiazol-2-ylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.16 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ12.90-11.20 (1H, br), 8.15 (1H, s), 8.11 (1H, d, J=8.0 Hz), 7.93 (2H, d,J=8.5 Hz), 7.48 (2H, d, J=8.5 Hz), 7.44-7.16 (5H, m), 5.92 (2H, brs),5.04 (2H, s), 4.87-4.50 (3H, m), 2.92-2.58 (2H, m).

EXAMPLE 6(155)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(3-nitrophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.28 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ13.30-11.70 (1H, br), 8.74 (1H, t, J=2.0 Hz), 8.40 (1H, s), 8.46-8.29(1H, m), 8.27-8.10 (1H, m), 8.09-7.91 (1H, m), 7.74 (1H, t, J=8.0 Hz),7.50-7.15 (5H, m), 6.00 (2H, brs), 5.09 (2H, s), 4.83 (2H, s), 4.78-4.50(1H, m), 2.94-2.55 (2H, m).

EXAMPLE 6(156)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(3-nitrophenyl)thiazol-2-ylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.13 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ8.72 (1H, t, J=2.0 Hz), 8.43 (1H, s), 8.45-8.29 (1H, m), 8.25-8.02 (2H,m), 7.73 (1H, t, J=8.0 Hz), 7.50-7.12 (5H, m), 5.90 (2H, brs), 5.05 (2H,s), 4.90-4.50 (3H, m), 2.95-2.55 (2H, m).

EXAMPLE 6(157)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethylcarbonylaminophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.10-10.50 (1H, br), 7.90 (1H, d, J=7.2 Hz), 7.75 (2H, d, J=8.8 Hz),7.55 (2H, d, J=8.8 Hz), 7.48-7.38 (6H, m), 5.94 (2H, brs), 5.09 (2H, s),4.70-4.47 (1H, m), 2.90-2.53 (2H, m).

EXAMPLE 6(158)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-trifluoromethylcarbonylaminophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol:acetic acid=18:1:1).

EXAMPLE 6(159)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imizazol-4-ylmethyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.37 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ9.07 (1H, s), 8.02 (1H, d, J=8.6 Hz), 7.51 (1H, s), 7.40-7.30 (5H, m),5.98 (2H, s), 5.09 (2H, s), 4.62 (1H, m), 4.43 (2H, s), 2.90-2.60 (2H,m).

EXAMPLE 6(160)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imizazol-4-ylmethyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.40 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ9.04 (1H, s), 8.13 (1H, d, J=8.6 Hz), 7.52 (1H, s), 7.40-7.30 (5H, m),5.86 (2H, brs), 5.11 (2H, s), 4.67 (1H, m), 4.31 (2H, s), 2.94-2.84 (2H,m).

EXAMPLE 7N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(carboxymethyl)tetrazol-2-yl)pentanoicacid

To a solution of the compound prepared in example 5(18) (59 mg) indimethoxyethane (1 ml) was added a 1 N aqueous solution of sodiumhydroxide (0.36 ml). The reaction mixture was stirred for 4 h at roomtemperature. The reaction mixture was quenched by addition of a 1Naqueous solution of hydrochloric acid, and extracted with ethyl acetate.The extract was washed with water and a saturated aqueous solution ofsodium chloride, dried over anhydrous sodium sulfate and concentrated.The residue was purified by column chromatography on silica gel(chloroform methanol:acetic acid=18:1:1) to give the compound of thepresent invention (32 mg) having the following physical data.

TLC:Rf 0.32 (chloroform:ethanol:acetic acid=8:1:1); NMR (DMSO-d₆): δ7.99 (1H, m), 7.42-7.24 (5H, m), 5.97 (2H, brs), 5.09 (2H, s), 4.62 (1H,m), 3.94 (2H, s), 2.91-2.54 (2H, m).

EXAMPLE 7(1)-7(3)

By the same procedure as provided in example 7, using the compoundsprepared in examples 5(21), 5(30) or 5(31) instead of the compoundprepared in example 5(18), compounds of the present invention having thefollowing physical data were obtained.

EXAMPLE 7(1)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(carboxymethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.30 (chloroform:ethanol:acetic acid=4:1:1); NMR (DMSO-d₆): δ8.07 (1H, m), 7.45-7.17 (5H, m), 5.73 (2H, br), 5.09 (2H, s), 4.63 (1H,m), 4.10-3.85 (2H, m), 2.88-2.58 (2H, m).

EXAMPLE 7(2)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-carboxyethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.54 (chloroform:methanol:acetic acid=10:1:1); NMR (DMSO-d₆): δ13.50-11.12 (2H, br), 7.96 (1H, d, J=7.6 Hz), 7.44-7.21 (5H, m), 5.89(2H, brs), 5.10 (2H, s), 4.74-4.52 (1H, m), 3.07 (2H, t, J=7.2 Hz),2.88-2.54 (4H, m).

EXAMPLE 7(3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-carboxyethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.44 (chloroform:methanol:acetic acid=10:1:1); NMR (DMSO-d₆): δ8.03-7.82 (1H, m), 7.52-7.17 (5H, m), 5.90-5.56 (2H, m), 5.10 (2H, s),4.71-4.40 (1H, m), 3.05-2.80 (2H, m), 2.80-2.37 (4H, m).

EXAMPLE 8(1)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylsulfinyltetrazol-1-yl)pentanoic acid.t-butylester

To a solution of the compound prepared in example 5(19) (50 mg) inmethanol (2.1 ml) and water (0.4 ml) was added a 20% aqueous solution oftitanium (III) chloride (0.2 ml). To the mixture was added dropwise asolution of a 30% aqueous solution of hydrogen peroxide (0.1 ml) inmethanol (0.5 ml). The reaction mixture was stirred for 15 min at roomtemperature. The reaction mixture was quenched by addition of water, andextracted with chloroform. The extract was dried over anhydrousmagnesium sulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl:acetate=4:1→1:1) to give thecompound of the present invention (38 mg) having the following physicaldata.

TLC:Rf 0.39 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.39 (5H, m),6.05-5.60 (3H, m), 5.19 (2H, s), 4.75 (1H, m), 3.35 (2H, m), 2.98 (1H,m), 2.74 (1H, m), 1.35 (12H, m).

EXAMPLE 8(2)-8(4)

By the same procedure as provided in example 8(1), using the compoundsprepared in examples 5(20), 5(22) or 5(23) instead of the compoundprepared in example 5(19), compounds of the present invention having thefollowing physical data were obtained.

EXAMPLE 8(2)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylsulfinyltetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.25 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.39 (5H, m),6.01 (1H, m), 5.88 (2H, m), 5.18 (2H, s), 4.69 (1H, m), 3.33 (2H, m),3.03 (1H, m), 2.73 (1H, m), 1.38 (12H, m).

EXAMPLE 8(3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylsulfinylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.12 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.40 (9H, m),5.98 (1H, d, J=10.0 Hz), 5.82 (1H, m), 5.64 (1H, m), 5.18 (2H, s), 4.65(1H, m), 4.44 (1H, d, J=17.5 Hz), 4.32 (1H, d, J=17.5 Hz), 3.01 (1H, m),2.72 (1H, m), 1.42 (9H, m).

EXAMPLE 8(4)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylsulfinylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.23 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.40 (9H, m),6.05-5.68 (3H, m), 5.20 (2H, s), 4.62 (1H, m), 4.40 (1H, m), 4.12 (1H,m), 3.06 (1H, m), 2.79 (1H, m), 1.42 and 1.38 (total 9H, each s).

EXAMPLE 9(1)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylsulfonyltetrazol-1-yl)pentanoic acid.t-butylester

To a solution of the compound prepared in example 5(19) (50 mg) indichloromethane (3 ml) and chloroform (3 ml) was added 80%m-chloroperbenzoic acid (48 mg) at 0° C. The reaction mixture wasstirred for 18 h at room temperature. The reaction mixture was quenchedby addition of water (10 ml), and extracted with chloroform. The extractwas washed with a saturated aqueous solution of sodium hydrocarbonate,water and a saturated aqueous solution of sodium chloride, successively,dried over anhydrous magnesium sulfate and concentrated. The residue waspurified by column chromatography on silica gel (hexane:ethylacetate=4:1→1:1) to give the compound of the present invention (25 mg)having the following physical data.

TLC:Rf 0.69 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.39 (5H, m),6.01 (1H, m), 5.95 (1H, d, J=16 Hz), 5.74 (1H, d, J=16 Hz), 5.20 (2H,s), 4.73 (1H, m), 3.50 (2H, q, J=7 Hz), 3.00 (1H, dd, J=17.5, 5 Hz),2.73 (1H, dd, J=17.5, 5 Hz), 1.42 (12H, m).

EXAMPLE 9(2)-9(4)

By the same procedure as provided in example 9(1), using the compoundsprepared in examples 5(20), 5(22) or 5(23) instead of the compoundprepared in example 5(19), compounds of the present invention having thefollowing physical data were obtained.

EXAMPLE 9(2)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylsulfonyltetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.73 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.40 (5H, m),6.00 (1H, d, J=16 Hz), 5.95 (1H, m), 5.80 (1H, d, J=16 Hz), 5.18 (2H,s), 4.69 (1H, m), 3.46 (2H, q, J=7 Hz), 3.05 (1H, dd, J=17.5, 5 Hz),2.73 (1H, dd, J=17.5, 5 Hz), 1.41 (12H, m).

EXAMPLE 9(3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylsulfonylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.30 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.68 (2H, d,J=9.0 Hz), 7.48 (2H, d, J=9.0 Hz), 7.40 (5H, m), 5.92 (1H, d, J=10.0Hz), 5.88 (1H, d, J=17.5 Hz), 5.66 (1H, d, J=17.5 Hz), 5.20 (2H, s),4.70 (2H, s), 4.65 (1H, m), 3.01 (1H, dd, J=17.5 Hz and 5.0 Hz), 2.72(1H, dd, J=17.5 Hz and 5.0 Hz), 1.42 (9H, s).

EXAMPLE 9(4)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylsulfonylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.39 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.60-7.30 (9H,m), 6.10-5.75 (3H, m), 5.20 (2H, s), 4.65 (3H, m), 3.10 (1H, dd, J=17.5Hz and 5.0 Hz), 2.82 (1H, dd, J=17.5 Hz and 5.0 Hz), 1.42 (9H, s).

EXAMPLE 10(1)-10(8)

By the same procedure as provided in example 6(1), using the compoundsprepared in examples 8(1)-8(4) or 9(1)-9(4), compounds of the presentinvention having the following physical data were obtained.

EXAMPLE 10(1)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylsulfinyltetrazol-1-yl)pentanoic acid

TLC:Rf 0.54 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ7.90 (1H, m), 7.35 (5H, m), 5.90 (2H, m), 5.10 (2H, s), 4.60 (1H, m),3.35 (2H, m), 2.70 (2H, m), 1.20 (3H, m).

EXAMPLE 10(2)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylsulfonyltetrazol-1-yl)pentanoic acid

TLC:Rf 0.58 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ7.90 (1H, m), 7.38 (5H, m), 5.95 (2H, m), 5.10 (2H, s), 4.60 (1H, m),3.70 (2H, m), 2.70 (2H, m), 1.25 (3H, m).

EXAMPLE 10(3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylsulfinyltetrazol-2-yl)pentanoic acid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ7.98 (1H, m), 7.35 (5H, m), 6.10 (2H, brs), 5.10 (2H, s), 4.63 (1H, m),3.35 (2H, m), 2.70 (2H, m), 1.19 (3H, m).

EXAMPLE 10(4)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-ethylsulfonyltetrazol-2-yl)pentanoic acid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ8.00 (1H, m), 7.35 (5H, m), 6.15 (2H, brs), 5.10 (2H, s), 4.65 (1H, m),3.64 (2H, m), 2.74 (2H, m), 1.21 (3H, m).

EXAMPLE 10(5)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylsulfinylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.41 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ7.73 (1H, m), 7.60 (4H, m), 7.38 (5H, m), 5.99 (2H, br), 5.08 (2H, s),4.60 (3H, m), 2.64 (2H, m).

EXAMPLE 10(6)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylsulfinylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.41 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ7.75 (1H, m), 7.60 (4H, m), 7.38 (5H, m), 5.85 (2H, m), 5.08 (2H, m),4.90 (1H, m), 4.58 (2H, m), 2.61 (2H, m).

EXAMPLE 10(7)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylsulfonylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.48 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ7.73 (4H, m), 7.60 (1H, m), 7.38 (5H, m), 6.01 (2H, br), 5.21 (2H, s),5.08 (2H, s), 4.55 (1H, m), 2.60 (2H, m).

EXAMPLE 10(8)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-chlorophenylsulfonylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.51 (chloroform:methanol:acetic acid=15:1:1); NMR (DMSO-d₆): δ7.79 (5H, m), 7.35 (5H, m), 5.88 (2H, m), 5.40 (2H, m), 5.08 (2H, s),4.52 (1H, m), 2.65 (2H, m).

EXAMPLE 11N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-trimethylsilyltetrazol-2-yl)pentanoic acid.t-butylester

To a solution of (S)-N-benzyloxycarbonyl-3-amino-3-methoxycarbonylpropanic acid.t-butylester (1.69 g) in tetrahydrofuran (10 ml) was addeddropwise a 2M lithium diisopropylamide [LDA] inheptane/tetrahydrofuran/ethylbenzene solution (2.5 ml) at 0° C. under anatmosphere of argon. To the mixture was added dropwise the solutionprepared in the mixture of trimethyldiazomethane (in 10% hexanesolution, 13.7 g) and 2M lithium diisopropylamide inheptane/tetrahydrofuran/ethylbenzene solution (6 ml) at 0° C. under anatmosphere of argon using cannula. The reaction mixture was stirred for3.5 h at 0° C. The mixture was poured into ice water, and extracted withdiethylether. The extract was washed with water and a saturated aqueoussolution of sodium chloride, successively, dried over anhydrous sodiumsulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=2:1) to give thecompound of the present invention (633 mg) having the following physicaldata.

TLC:Rf 0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.36 (5H, m),5.97 (1H, m), 5.87 and 5.68 (each 1H, both d, J=17.5 Hz), 5.16 (2H,brs), 4.67 (1H, m), 3.00 (1H, dd, J=16.0, 4.5 Hz), 2.70 (1H, dd, J=16.0,5.0 Hz), 1.41 (9H, s), 0.39 (9H, s).

EXAMPLE 12N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-trimethylsilyltetrazol-2-yl)pentanoic acid

By the same procedure as provided in example 6(1), using the compoundprepared in example 11, compound of the present invention having thefollowing physical data was obtained.

TLC:Rf 0.29 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 7.56 (1H, m),7.34 (5H, m), 5.98 (2H, m), 5.06 (2H, s), 4.52 (1H, m), 2.58 (2H, m),0.34 (9H, s).

REFERENCE EXAMPLE 8N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)ethenyl)tetrazol-2-yl)pentanoicacid.t-butylester (1) andN-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)ethenyl)tetrazol-1-yl)pentanoicacid.t-butylester (2)

To a solution of N-benzyloxycarbonyl-3-amino-4-oxo-5-bromopentanoicacid.t-butylester (300 mg) in N,N-dimethylformamide (5 ml) was addedpotassium carbonate (414 mg) and 5-(2-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)ethenyl)tetrazole (438 mg). The reactionmixture was stirred for 4 h at room temperature. The reaction mixturewas quenched by addition of a saturated aqueous solution of sodiumhydrocarbonate, and extracted with ethyl acetate. The extract was washedwith a saturated aqueous solution of sodium chloride, dried overanhydrous sodium sulfate and concentrated. The residue was purified bycolumn chromatography on silica gel (hexane:ethyl acetate=1:1) to givethe compound of reference example 8(1) (297 mg) and reference example8(2) (110 mg), respectively.

REFERENCE EXAMPLE 8(1)

TLC:Rf 0.61 (hexane:ethyl acetate=1:4); NMR (CDCl₃): δ 7.67 (1H, d, J=16Hz), 7.61 (1H, d, J=16 Hz), 7.38 (5H, m), 7.17 (1H, d, J=1.2 Hz), 7.07(1H, d, J=1.2 Hz), 5.99 (1H, d, J=8.8 Hz), 5.83 (1H, d, J=18 Hz), 5.67(1H, d, J=18 Hz), 5.38 (2H, s), 5.19 (2H, s), 4.66 (1H, m), 3.53 (2H, t,J=8.0 Hz), 3.03 (1H, dd, J=4.6, 18 Hz), 2.73 (1H, dd, J=4.8, 18 Hz),1.43 (9H, s), 0.91 (2H, t, J=8.0 Hz), −0.03 (9H, s).

REFERENCE EXAMPLE 8(2)

TLC:Rf 0.50 (hexane:ethyl acetate=1:4); NMR (CDCl₃): δ 7.83 (1H, d, J=16Hz), 7.40-7.08 (8H, m), 6.02 (1H, d, J=9.0 Hz), 5.73 (1H, d, J=19 Hz),5.52 (1H, d, J=19 Hz), 5.38 (2H, s), 5.21 (2H, s), 4.70 (1H, m), 3.51(2H, t, J=8.2 Hz), 3.06 (1H, dd, J=4.8, 17 Hz), 2.74 (1H, dd, J=4.8, 17Hz), 1.39 (9H, s), 0.91 (2H. t, J=8.2 Hz), −0.03 (9H, s).

REFERENCE EXAMPLE 8(3)-8(12)

By the same procedure as provided in reference example 8, using thecorresponding tetrazole compound instead of 5-(2-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)ethenyl)tetrazole, the title compounds havingthe following physical data were obtained.

REFERENCE EXAMPLE 8(3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)ethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.58 (chloroform:t-butanol=10:1); NMR (CDCl₃): δ 7.38 (5H, m),6.94 (1H, d, J=1.2 Hz), 6.90 (1H, d, J=1.2 Hz), 6.29 (1H, d, J=8.6 Hz),5.71 (1H, d, J=18 Hz), 5.61 (1H, d, J=18 Hz), 5.21 (2H, s), 5.17 (2H,s), 4.60 (1H, m), 3.54-3.38 (4H, m), 3.30-3.18 (2H,m), 2.96 (1H, dd,J=4.6, 17 Hz), 2.75 (1H, dd, J=4.8, 17 Hz), 1.42 (9H, s), 0.90 (2H, t,J=8.2 Hz), −0.02 (9H, s).

REFERENCE EXAMPLE 8(4)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)ethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.50 (chloroform;t-butanol=10:1); NMR (CDCl₃): δ 7.38 (5H, m),6.85 (1H, d, J=1.2 Hz), 6.82 (1H, d, J=1.2 Hz), 6.17 (1H, d, J=9.0 Hz),5.81 (1H, d, J=19 Hz), 5.60 (1H, d, J=19 Hz), 5.20 (2H, s), 5.16 (2H,s), 4.66 (1H, m), 3.44 (2H, t, J=8.2 Hz), 3.30-3.18 (4H, m), 3.03 (1H,dd, J=4.8,17 Hz), 2.74 (1H, dd, J=4.8, 17 Hz), 1.40 (9H, s), 0.88 (2H,t, J=8.2 Hz), −0.02 (9H, s).

REFERENCE EXAMPLE 8(5)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.45 (chloroform:t-butanol=15:1); NMR (CDCl₃): δ 7.70-7.60 (2H,m), 7.40-7.28 (7H, m), 7.12-7.08 (2H, m), 6.04 (1H, m), 5.80-5.74 (2H,m, ), 5.25 (2H, s), 5.16 (2H, s), 4.32 (1H, m), 4.32 (2H, s), 3.54 (2H,t, J=8.0 Hz), 3.04-2.62 (2H, m), 1.41 (9H, s), 0.91 (2H, t, J=8.0 Hz),0.00 (9H, s).

REFERENCE EXAMPLE 8(6)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)phenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.38 (chloroform:t-butanol:acetic acid=15:1); NMR (CDCl₃): δ 7.86(1H, m), 7.70-7.60 (2H, m), 7.42-7.28 (7H, m), 7.10 (2H, m), 5.44-5.20(4H, m), 5.13 (2-H, s), 4.64 (1H, m), 4.23 (2H, s), 3.56 (2H, t, J=8.0Hz), 2.80-2.70 (2H, m), 1.40 (9H, s), 0.93 (2H, t, J=8.0 Hz), 0.00 (9H,s).

REFERENCE EXAMPLE 8(7)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.51 (chloroform:methanol=15:1); NMR (CDCl₃): δ 7.73 (2H, d,J=8.2 Hz), 7.40-7.32 (7H, m), 7.12 (1H, d, J=1.4 Hz), 7.09 (1H, d, J=1.4Hz), 6.02 (1H, d, J=9.2 Hz), 5.78 (1H, d, J=18 Hz), 5.63 (1H, d, J=18Hz), 5.25 (2H, s), 5.16 (2H, s), 4.64 (1H, m), 4.31 (2H, s), 3.56 (2H,t, J=8.2 Hz), 3.05 (1H, dd, J=4.4, 17 Hz), 2.96 (1H, dd, J=4.4, 17 Hz),1.42 (9H, s), 0.90 (2H, t, J=8.2 Hz), −0.02 (9H, s).

REFERENCE EXAMPLE 8(8)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)phenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.46 (chloroform:methanol=15:1); NMR (CDCl₃): δ 7.77 (2H, d,J=8.2 Hz), 7.40-7.29 (7H, m), 7.13 (1H, d, J=1.2 Hz), 7.10 (1H, d, J=1.2Hz), 5.81 (1H, d, J=9.2 Hz), 5.38 (2H, s), 5.24 (2H, s), 5.14 (2H, s),4.58 (1H, m), 4.26 (1H, d, J=16 Hz), 4.09 (1H, d, J=16Hz), 3.58 (2H, t,J=8.2 Hz), 3.07 (1H, dd, J=4.4, 18 Hz ), 2.74 (1H, dd, J=4.4, 17 Hz),1.43 (9H, s), 0.92 (2H, t, J=8.2 Hz), −0.01 (9H, s).

REFERENCE EXAMPLE 8(9)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.51 (chloroform:methanol=15:1); NMR (CDCl₃): δ 7.54-7.20 (11H,m), 6.36 (1H, m), 5.80-5.44 (2H, m), 5.15 (2H, s), 5.02-4.96 (2H, m),4.62 (1H, m), 4.50-4.40 (2H, m), 3.54 (2H, t, J=8.2 Hz), 2.98-2.74 (2H,m), 1.41 (9H, s), 0.90 (2H, t, J=8.2 Hz), 0.00 (9H, s).

REFERENCE EXAMPLE 8(10)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-yl)phenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.64 (chloroform:methanol=15:1); NMR (CDCl₃): δ 7.62-7.15 (11H,m), 6.90 (1H, m), 5.86-5.46 (2H, m), 5.23-5.20 (4H, m), 4.84 (1H, m),4.60-4.20 (2H, m), 3.66 (2H, t, J=8.2 Hz), 3.02-2.78 (2H, m), 1.41 (9H,s), 0.98 (2H. t, J=8.2 Hz), 0.02 (9H, s).

REFERENCE EXAMPLE 8(11)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.47 (chloroform:methanol=15:1); NMR (CDCl₃): δ 7.40-7.30 (5H,m), 6.95 (2H, br-s), 6.10 (1H, d, J=8.0 Hz), 5.80-5.58 (2H, m), 5.30(2H, s), 5.15 (2H, s), 4.60 (1H, m), 4.47 (2H, s), 3.48 (2H, t, J=8.2Hz), 2.96 (1H, dd, J=4.8, 17 Hz), 2.71 (1H, dd, J=5.0, 17 Hz), 1.41 (9H,s), 0.88 (2H, t, J=8.2 Hz), −0.01 (9H, s).

REFERENCE EXAMPLE 8(12)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-(2-(trimethylsilyl)ethoxymethyl)imidazol-2-ylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.57 (chloroform:methanol=15:1); NMR (CDCl₃): δ 7.40-7.30 (5H,m), 6.92 (1H, d, J=1.2 Hz), 6.87 (1H, d, J=1.2 Hz), 6.38 (1H, d, J=8.0Hz), 5.82 (1H, d, J=18 Hz), 5.82 (1H, d, J=18 Hz), 5.36-5.18 (4H, m),4.76 (1H, m), 4.40 (2H, s), 3.43 (2H, t, J=8.2 Hz), 2.93 (1H, dd, J=4.6,17 Hz), 2.72 (1H, dd, J=5.2, 17 Hz), 1.40 (9H, s), 0.87 (2H, t,J=8.2Hz), −0.02 (9H, s).

EXAMPLE 13(1)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)ethenyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

By the same procedure as provided in example 6(1), using the compoundprepared in reference example 8(1), compound of the present inventionhaving the following physical data was obtained.

TLC:Rf 0.28 (chloroform:methanol:acetic acid=10:2:1); NMR (DMSO-d₆): δ8.18-8.04 (2H, m), 7.69 (2H, s), 7.63 (1H, d, J=17 Hz), 7.42-7.30 (5H,m), 6.07 (2H, s), 5.10 (2H, s), 4.64 (1H, m), 2.92-2.60 (2H, m).

EXAMPLE 13(2)-13(12)

By the same procedure as provided in reference example 8→example 13(1),and if necessary, by known methods converted to accommodate thecorresponding salts, using the corresponding tetrazole compound insteadof5-(2-(1-((2-trimethylsilyl)ethoxymethyl)imidazol-2-yl)ethenyl)tetrazole,compounds of the present invention having the following physical datawere obtained.

EXAMPLE 13(2)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)ethenyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.50 (chloroform:methanol:acetic acid=10:2:1); NMR (DMSO-d₆): δ8.16-8.02 (2H, m), 7.70-7.60 (3H, m), 7.42-7.30 (5H, m), 6.02-5.80 (2H,m), 5.12 (2H, s), 4.84 (1H, m), 3.00-2.60 (2H, m).

EXAMPLE 13(3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)ethyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.29 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ8.02 (1H, m), 7.53 (2H, s), 7.40-7.30 (5H, m), 5.82 (2H, brs), 5.09 (2H,s), 4.60 (1H, m), 3.50-3.40 (4H, m), 2.90-2.60 (2H, m).

EXAMPLE 13(4)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)ethyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.40 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ8.10 (1H, d, J=8.6 Hz), 7.52 (2H, s), 7.40-7.30 (5H, m), 5.79 (2H, brs),5.09 (2H, s), 4.64 (1H, m), 3.42-3.32 (4H, m), 2.92-2.60 (2H, m).

EXAMPLE 13(5) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-(imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.51 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ8.04-7.96 (3H, m), 7.52-7.28 (9H, m), 5.90 (2H, m), 5.08 (2H, s), 4.60(1H, m), 4.32 (2H, s), 2.90-2.60 (2H, m).

EXAMPLE 13(6) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-(imidazol-2-yl)phenylmethyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.60 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ8.12 (1H, m), 8.02-7.90 (2H, m), 7.50-7.20 (9H, m), 5.79 (2H, m), 5.09(2H, s), 4.64 (1H, m), 4.20 (2H, s), 2.90-2.62 (2H, m).

EXAMPLE 13(7) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.46 (chloroform:methanol:acetic acid=10:4:1); NMR (DMSO-d₆): δ8.18 (2H, d, J=8.6 Hz), 8.04 (1H, d, J=7.8 Hz), 7.77 (2H, s), 7.54 (2H,d, J=8.6 Hz), 7.42-7.26 (5H, m), 5.70 (2H, brs), 5.09 (2H, s), 4.62 (1H,m), 4.39 (2H, brs), 2.90-2.56 (2H, m).

EXAMPLE 13(8) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(imidazol-2-yl)phenylmethyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.40 (chloroform:methanol acetic acid=10:4:1); NMR (DMSO-d₆): δ8.22-8.12 (3H, m), 7.77 (2H, s), 7.52 (2H, d, J=8.6 Hz), 7.42-7.30 (5H,m), 5.86 (2H, brs), 5.10 (2H, s), 4.64 (1H, m), 4.25 (2H, brs),2.92-2.64 (2H, m).

EXAMPLE 13(9) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.44 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ8.02 (1H, m), 7.72-7.24 (11H, m), 5.85 (2H, brs), 5.08 (2H, s) 4.62-4.62(3H, m), 2.88-2.58 (2H, m).

EXAMPLE 13(10) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)phenylmethyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.58 (chloroform:methanol:acetic acid=10:3:1); NMR (DMSO-d₆): δ8.12 (1H, m), 7.68-7.30 (11H, m), 5.82 (2H, brs), 5.11 (2H, s),4.70-4.58 (3H, m), 2.92-2.60 (2H, m).

EXAMPLE 13(11)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imidazol-2-ylmethyl)tetrazol-2-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.41 (chloroform:methanol:water=10:5:1); NMR (DMSO-d₆): δ 8.04(1H, m), 7.59 (2H, s), 7.40-7.30 (5H, m), 6.01 (2H, brs), 5.08 (2H, s),4.73 (2H, s), 4.62 (1H, m), 2.92-2.58 (2H, m).

EXAMPLE 13(12)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imidazol-2-ylmethyl)tetrazol-1-yl)pentanoic acid.hydrochloric acid salt

TLC:Rf 0.55 (chloroform:methanol:water=10:5:1); NMR (DMSO-d₆): δ 8.14(1H, m), 7.60 (2H, s), 7.40-7.30 (5H, m), 5.91 (2H, brs,), 5.11 (2H,s,), 4.80-4.60 (3H, m), 2.92-2.62 (2H, m).

EXAMPLE 14(1)-14(106)

By the same procedure as provided in example 1, using the correspondingtetrazole compounds and the corresponding bromo compounds instead ofN-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-bromopentanoicacid.t-butylester, compounds of the present invention having thefollowing physical data were obtained.

EXAMPLE 14(1)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.36 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.40-7.12 (8H,m), 6.62 (1H, d, J=9.5 Hz), 5.69 and 5.49 (each 1H, d, J=17.8 Hz),4.95-4.78 (1H, m), 4.60 (4H, s), 4.19 (2H, s), 2.98 (1H, dd, J=17.5 Hz,4.4 Hz), 2.66 (1H, dd, J=17.5 Hz, 4.8 Hz), 1.41 (3H, s).

EXAMPLE 14(2)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.15 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.41-7.15 (8H,m), 6.52 (1H, d, J=9.5 Hz), 5.58 and 5.46 (each 1H, d, J=18.0 Hz),4.92-4.74 (1H, m), 4.33 and 4.23 (each 1H, d, J=17.5 Hz), 4.22 (2H, s),3.07 (1H, dd, J=17.5 Hz, 5.0 Hz), 2.75 (1H, dd, J=17.5 Hz, 5.5 Hz), 1.41(3H, s).

EXAMPLE 14(3)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.72 (benzene:diethylether=2:1); NMR (CDCl₃): δ 7.45 (2H, d,J=6.8 Hz), 7.35-7.20 (6H, m), 6.61 (1H, d, J=8.8 Hz), 5.67 (1H, d,J=17.8 Hz), 5.48 (1H, d, J=17.8 Hz), 4.90-4.80 (1H, m), 4.19 (2H, s),2.99 (1H, dd, J=4.4, 17.4 Hz), 2.67 (1H, dd, J=5.0, 17.6 Hz), 1.41 (9H,s).

EXAMPLE 14(4)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.57 (benzene:diethylether=2:1); NMR (CDCl₃): δ 7.47-7.20 (8H,m), 6.66 (1H, d, J=8.8 Hz), 5.58 (1H, d, J=18.2 Hz), 5.42 (1H, d, J=18.2Hz), 4.95-4.83 (1H, m), 4.23 (2H, s), 3.06 (1H, dd, J=4.4, 17.6 Hz),2.73 (1H, dd, J=4.6, 17.6 Hz), 1.44 (9H, s).

EXAMPLE 14(5)N-(2-phenylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.22 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.37-7.11 (8H,m), 5.80 (1H, d, J=9.4 Hz), 5.65 (1H, d, J=17.9 Hz), 5.44 (1H, d, J=17.9Hz), 4.61-4.14 (4H, m), 3.05-2.93 (3H, m), 2.65 (1H, dd, J=4.6, 17.2Hz), 1.41 (9H, s).

EXAMPLE 14(6)N-(2-phenylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.77 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.39-7.17 (8H,m), 5.74 (1H, d, J=9.0 Hz), 5.59 (1H, d, J=18.8 Hz), 5.43 (1H, d, J=18.8Hz), 4.54-4.28 (4H, m), 3.14-2.97 (3H, m), 2.73 (1H, dd, J=5.0, 19.0Hz), 1.42 (9H, s).

EXAMPLE 14(7)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.58 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.37-7.09 (8H,m), 6.58 (1H, d, J=8.8 Hz), 5.67 (1H, d, J=17.8 Hz), 5.45 (1H, d, J=17.8Hz), 4.89-4.80 (1H, m), 4.61 (2H, s), 3.28-3.19 (2H, m), 3.03-2.87 (3H,m), 2.65 (1H, dd, J=4.6, 17.4 Hz), 1.42 (9H, s).

EXAMPLE 14(8)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.35 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.39-7.15 (8H,m), 6.53 (1H, d, J=8.6 Hz), 5.61 (1H, d, J=18.7 Hz), 5.46 (1H, d, J=18.7Hz), 4.87-4.78 (1H, m), 4.37 (1H, d, J=14.9 Hz), 4.26 (1H, d, J=18.7Hz), 3.31-3.23 (2H, m), 3.13-2.90 (3H, m), 2.74 (1H, dd, J=4.9, 17.6Hz), 1.43 (9H, s).

EXAMPLE 14(9)N-(2,6-dichlorobenzyloxy)carbonyl-3-amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.50 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.41-7.20 (8H,m), 5.76 (1H, d, J=9.0 Hz), 5.66-5.11 (4H, m), 4.60-4.50 (1H, m),4.32-4.03 (2H, m), 3.07 (1H, dd, J=4.4, 17.6 Hz), 2.73 (1H, dd, J=4.8,17.6 Hz), 1.44 (9H, s).

EXAMPLE 14(10)N-(2,6-dichlorobenzyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.44 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.39-7.13 (6H,m), 5.92 (1H, d, J=8.4 Hz), 5.86-5.47 (4H, m), 4.68-4.55 (1H, m), 4.60(2H, s), 3.03 (1H, dd, J=4.2, 17.0 Hz), 2.71 (1H, dd, J=4.6, 17.0 Hz),1.40 (9H, s).

EXAMPLE 14(11)N-(3-phenylpropyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.50 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.36-7.13 (8H,m), 5.83 (1H, d, J=8.8 Hz), 5.79 (1H, d, J=17.8 Hz), 5.60 (1H, d, J=17.8Hz), 4.15 (2H, t, J=6.6 Hz), 2.98 (1H, dd, J=4.7, 17.5 Hz), 2.74-2.63(3H, m), 2.04-1.94 (2H, m), 1.43 (9H, s).

EXAMPLE 14(12)N-(3-phenylpropyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.24 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.39-7.17 (8H,m), 5.77 (1H, d, J=8.6 Hz), 5.72 (1H, d, J=18.8 Hz), 5.57 (1H, d, J=18.8Hz), 4.37 (1H, d, J=15.6 Hz), 4.26 (1H, d, J=15.6 Hz), 4.19 (2H, t,J=6.6 Hz), 3.11 (1H, dd, J=4.6, 17.4 Hz), 2.82-2.69 (3H, m), 2.08-1.94(2H, m), 1.43 (9H, s).

EXAMPLE 14(13)N-(4-phenylbutyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.51 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.37-7.13 (8H,m), 5.82 (1H, d, J=8.8 Hz), 5.78 (1H, d, J=17.8 Hz), 5.59 (1H, d, J=17.8Hz), 4.18-4.10 (2H, br), 2.99 (1H, dd, J=4.6, 11.5 Hz), 2.74-2.62 (3H,m), 1.72-1.66 (4H, m), 1.42 (9H, s).

EXAMPLE 14(14)N-(4-phenylbutyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.28 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.39-7.15 (8H,m), 5.76 (1H, d, J=8.8 Hz), 5.72 (1H, d, J=18.8 Hz), 5.57 (1H, d, J=18.8Hz), 4.37 (1H, d, J=15.6 Hz), 4.26 (1H, d, J=15.6 Hz), 4.22-4.14 (2H,br), 3.08 (1H, dd, J=4.6,17.4 Hz), 2.81-2.63 (3H, m), 1.75-1.68 (4H, m),1.42 (9H, s).

EXAMPLE 14(15)N-(2-(thiophen-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.38 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.39-7.35 (2H,m), 7.27-7.14 (2H, m), 6.97-6.89 (2H, m), 5.85 (1H, d, J=9.2 Hz), 5.73(1H, d, J=17.8 Hz), 5.53 (1H, d, J=17.8 Hz), 4.64-4.21 (5H, m), 3.21(2H, t, J=6.6 Hz), 3.09 (1H, dd, J=4.5, 17.6 Hz), 2.75 (1H, dd, J=4.8,17.6 Hz), 1.42 (9H, s).

EXAMPLE 14(16)N-(2-(thiophen-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.17 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.39-7.35 (2H,m), 7.26-7.14 (2H, m), 6.97-6.89 (2H, m), 5.85 (1H, d, J=9.2 Hz), 5.67(1H, d, J=18.8 Hz), 5.51 (1H, d, J=18.8 Hz), 4.64-4.22 (5H, m), 3.21(2H, t, J=6.6 Hz), 3.09 (1H, dd, J=4.5, 17.6 Hz), 2.75 (1H, dd, J=4.8,17.6 Hz), 1.42 (9H, s).

EXAMPLE 14(17)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.36 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.37-7.32 (2H,m), 7.21-7.12 (3H, m), 6.86-6.79 (2H, m), 5.82 (1H, d, J=9.2 Hz), 5.69(1H, d, J=17.9 Hz), 5.49 (1H, d, J=17.9 Hz), 4.61-4.54 (3H, m),4.45-4.21 (2H, m), 3.73 (3H, s), 3.02-2.86 (3H, m), 2.66 (1H, dd, J=4.6,17.2 Hz), 1.42 (9H, s).

EXAMPLE 14(18)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.19 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.39-7.35 (2H,m), 7.26-7.13 (3H, m), 6.88-6.81 (2H, m), 5.76 (1H, d, J=8.4 Hz), 5.62(1 HI d, J=i 8.8 Hz), 5.45 (1H, d, J=18.8Hz), 4.64-4.23 (5H, m), 3.74(3H, s), 2.93 (2H, t, J=7.0 Hz), 3.07 (1H, dd, J=4.4, 17.6 Hz), 2.66(1H, dd, J=4.6, 17.6 Hz), 1.42 (9H, s).

EXAMPLE 14(19)N-(2-(4-fluorophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.38 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.37-7.31 (2H,m), 7.21-7.13 (3H, m), 7.02-6.94 (2H, m), 5.81 (1H, d, J=8.6 Hz), 5.71(1H, d, J=17.8 Hz), 5.53 (1H, d, J=17.8 Hz), 4.61-4.55 (3H, m),4.43-4.23 (2H, m), 3.01-2.89 (3H, m), 2.66 (1H, dd, J=4.9, 17.6 Hz),1.42 (9H, s).

EXAMPLE 14(20)N-(2-(4-fluorophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.17 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.39-7.35 (2H,m), 7.24-7.16 (3H, m), 7.05-6.95 (2H, m), 5.76 (1H, d, J=8.4 Hz), 5.66(1H, d, J=18.8 Hz), 5.51 (1H, d, J=18.8 Hz), 4.65-4.55 (1H, m),4.43-4.23 (4H, m), 3.12-2.93 (3H, m), 2.74 (1H, dd, J=4.7, 17.5 Hz),1.42 (9H, s).

EXAMPLE 14(21)N-(2-(phenylmethyloxy)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.40 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.36-7.13 (8H,m), 5.95 (1H, d, J=8.7 Hz), 5.79 (1H, d, J=18.0 Hz), 5.57 (1H, d, J=18.0Hz), 4.66-4.57 (5H, m), 4.37-4.27 (2H, m), 3.69 (2H, t, J=4.6 Hz), 3.01(1H, dd, J=4.2, 17.5 Hz), 2.67 (1H, dd, J=4.3, 17.5 Hz), 1.42 (9H, s).

EXAMPLE 14(22)N-(2-(phenylmethyloxy)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.22 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.39-7.18 (8H,m), 5.90 (1H, d, J=8.8 Hz), 5.71 (1H, d, J=18.8 Hz), 5.56 (1H, d, J=18.8Hz), 4.65-4.56 (3H, m), 4.38-4.21 (4H, m), 3.73 (2H, t, J=4.4 Hz), 3.14(1H, dd, J=4.2, 17.7 Hz), 2.75 (1H, dd, J=4.8, 17.7 Hz), 1.42 (9H, s).

EXAMPLE 14(23)N-(2-(4-dimethylaminophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.60 (benzene diethylether=2:1); NMR (CDCl₃): δ 7.36-7.07 (5H,m), 6.65 (2H, d, J=8.8 Hz), 5.80 (1H, d, J=10.2 Hz), 5.67 (1H, d, J=17.8Hz), 5.45 (1H, d, J=17.8 Hz), 4.60 (2H, s), 4.62-4.55 (1H, m), 4.50-4.18(2H, m), 2.94-2.60 (4H, m), 2.84 (6H, s), 1.41 (9H, s).

EXAMPLE 14(24)N-(2-(4-dimethylaminophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.41 (benzene:diethylether=2:1); NMR (CDCl₃): δ 7.38-7.07 (5H,m), 6.68 (2H, d, J=8.8 Hz), 5.80 (1H, d, J=10.2 Hz), 5.67 (1H, d, J=17.8Hz), 5.45 (1H, d, J=17.8 Hz), 4.60 (2H, s), 4.62-4.55 (1H, m), 4.50-4.18(2H, m), 2.94-2.60 (4H, m), 2.84 (6H, s), 1.41 (9H, s).

EXAMPLE 14(25)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

NMR (CDCl₃): δ 7.49 (1H, d, J=8.8 Hz), 7.40 (1H, d, J=8.8 Hz), 7.36-7.22(5H, m), 6.64 (1H, d, J=8.8 Hz), 5.70 (1H, d, J=17.8 Hz), 5.50 (1H, d,J=17.8 Hz), 4.87 (1H, m), 4.20 (2H, s), 2.99 (1H, dd, J=17.4 Hz, 4.5Hz), 2.68 (1H, dd, J=17.4 Hz, 4.8 Hz), 1.41 (9H, s).

EXAMPLE 14(26)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

NMR (CDCl₃): δ 7.51 (1H, d, J=8.7 Hz), 7.40 (1H, d, J=8.7 Hz), 7.39-7.23(5H, m), 6.67 (1H, d, J=8.4 Hz), 5.61 (1H, d, J=18.5 Hz), 5.51 (1H, d,J=18.5 Hz), 4.92 (1H, m), 4.24 (2H, s), 3.08 (1H, dd, J=7 Hz, 4.0 Hz),2.73 (1H, dd, J=17 Hz, 4.8 Hz), 1.44 (9H, s).

EXAMPLE 14(27)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.53 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.36-7.22 (7H,m), 6.64 (1H, d, J=8.5 Hz), 5.68 (1H, d, J=17.8 Hz), 5.49 (1H, d, J=17.8Hz), 4.88 (1H, m), 4.20 (2H, s), 2.98 (1H, dd, J=17.3 Hz, 4.4 Hz), 2.67(1H, dd, J=17.3 Hz, 4.7 Hz), 2.34 (3H, s), 1.41 (9H, s).

EXAMPLE 14(28)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.39-7.23 (7H,m), 6.69 (1H, d, J=8.7 Hz), 5.58 (1H, d, J=18.4 Hz), 5.42 (1H, d, J=18.4Hz), 4.91 (1H, m), 4.24 (2H, s), 3.07 (1H, dd, J=17.5 Hz, 4.3 Hz), 2.72(1H, dd, J=17.5 Hz, 4.7 Hz), 2.34 (3H, s), 1.43 (9H, s).

EXAMPLE 14(29)N-(3-phenylpropylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.54 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.36-7.13 (8H,m), 6.59 (1H, d, J=8.8 Hz), 5.77 (1H, d, J=17.8 Hz), 5.57 (1H, d, J=17.8Hz), 4.91-4.82 (1H, m), 4.60 (2H, s), 3.04-2.91 (3H, m), 2.75-2.62 (3H,m), 2.05-1.90 (2H, m), 1.42 (9H, s).

EXAMPLE 14(30)N-(3-phenylpropylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.24 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.39-7.17 (8H,m), 6.53 (1H, d, J=8.6 Hz), 5.68 (1H, d, J=18.7 Hz), 5.54 (1H, d, J=18.7Hz), 4.89-4.81 (1H, m), 4.38 (1H, d, J=16.3 Hz), 4.27 (1H, d, J=16.3Hz), 3.31-2.97 (3H, m), 2.82-2.70 (3H, m), 2.07-1.93 (2H, m), 1.43 (9H,s).

EXAMPLE 14(31)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.38 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.41-7.16 (5H,m), 6.72 (2H, s), 6.66 (1H, d, J=8.6 Hz), 5.66 (1H, d, J=17.6 Hz), 5.48(1H, d, J=17.6 Hz), 4.95-4.76 (1H, m), 4.19 (2H, s), 2.99 (6H, s), 2.97(1H, dd, J=17.2 and 4.6 Hz), 2.68 (1H, dd, J=17.2 and 4.8 Hz), 1.41 (9H,s).

EXAMPLE 14(32)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.28 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.43-7.18 (5H,m), 6.70 (2H, s), 6.76-6.60 (1H, m), 5.55 (1H, d, J=18.2 Hz), 5.37 (1H,d, J=18.2 Hz), 4.99-4.80 (1H, m), 4.24 (2H, s), 3.15-2.96 (1H, m), 2.99(6H, s), 2.71 (1H, dd, J=17.4 and 4.8 Hz), 1.43 (9H, s).

EXAMPLE 14(33)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.58 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.49 (1H, d,J=8.8 Hz), 7.40 (1H, d, J=8.8 Hz), 7.30-7.21 (5H, m), 6.62 (1H, d, J=9Hz), 5.68 (1H, d, J=17.8 Hz), 5.46 (1H, d, J=17.8 Hz), 4.84 (1H, m),3.30-3.13 (2H, m), 3.05-2.90 (3H, m), 2.80-2.61 (1H, m), 1.42 (9H, s).

EXAMPLE 14(34)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.47 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.52 (1H, d,J=8.8 Hz), 7.40 (1H, d, J=8.8 Hz), 7.35-7.19 (5H, m), 6.65 (1H, d, J=8.7Hz), 5.61 (1H, d, J=18.5 Hz), 5.43 (1H, d, J=18.5 Hz), 4.91 (1H, m),3.33-3.25 (2H, m), 3.09 (1H, dd, J=17.6 Hz, 4.7 Hz), 3.01-2.93 (2H, m),2.72 (1H, dd, J=17.6 Hz, 4.7 Hz), 1.45 (9H, s).

EXAMPLE 14(35)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.56 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.32-7.14 (7H,m), 6.60 (1H, d, J=7.0 Hz), 5.65 (1H, d, J=17.9 Hz), 5.44 (1H, d, J=17.9Hz), 4.83 (1H, m), 3.29-3.20 (2H, m), 3.04-2.89 (3H, m), 2.65 (1H, dd,J=17.4 Hz, 4.7 Hz), 2.35 (3H, s), 1.42 (9H, s).

EXAMPLE 14(36)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:1);

NMR (CDCl₃): δ 7.31-7.19 (7H, m), 6.64 (1H, d, J=8.8 Hz), 5.58 (1H, d,J=18.5 Hz), 5.39 (1H, d, J=18.5 Hz), 4.90 (1H, m), 3.33-3.24 (2H, m),3.12-2.93 (3H, m), 2.71 (1H, dd, J=17.5 Hz, 4.8 Hz), 2.34 (3H, s), 1.44(9H, s).

EXAMPLE 14(37)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid-t-butylester

TLC:Rf 0.65 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.36-7.18 (5H,m), 6.63 (2H, d, J=8.8 Hz), 6.49 (2H, s), 5.64 (1H, d, J=18 Hz), 5.45(1H, d, J=18 Hz), 4.85 (1H, m), 4.18 (2H, s), 3.01-2.89 (7H, m), 2.65(1H, dd, J=4.6, 17 Hz), 2.44 (6H, s), 1.40 (9H, s).

EXAMPLE 14(38)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.50 (hexane:ethyl:acetate=3:2); NMR (CDCl₃): δ 7.40-7.20 (5H,m), 6.58 (2H, d, J=8.8 Hz), 6.49 (2H, s), 5.41 (1H, d, J=18 Hz), 5.24(1H, d, J=18 Hz), 4.83 (1H, m), 4.23 (2H, s), 3.05-2.94 (7H, m), 2.67(1H, dd, J=4.6, 17 Hz), 2.37 (6H, s), 1.43 (9H, s).

EXAMPLE 14(39)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.61 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.37-7.19 (5H,m), 7.16 (2H, s), 6.62 (1H, d, J=8.8 Hz), 5.65 (1H, d, J=17.7 Hz), 5.46(1H, d, J=17.7 Hz), 4.94-4.78 (1H, m), 4.19 (2H, s), 2.98 (1H, dd,J=17.5, 4.3 Hz), 2.65 (1H, dd, J=17.5, 4.7 Hz), 2.48 (6H, s), 1.41 (9H,s), 1.30 (9H, s).

EXAMPLE 14(40)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.47 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.42-7.13 (7H,m), 6.75-6.59 (1H, m), 5.48 (1H, d, J=18.5 Hz), 5.30 (1H, d, J=18.5 Hz),4.92-4.76 (1H, m), 4.24 (2H, s), 3.04 (1H, dd, J=17.5, 4.3 Hz), 2.68(1H, dd, J=17.5, 4.5 Hz), 2.41 (3H, s), 1.43 (9H, s), 1.30 (9H, s).

EXAMPLE 14(41)N-(2-(pyridin-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.33 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 8.53 (1H, d,J=5.0 Hz), 7.64-7.56 (1H, m), 7.36-7.08 (5H, m), 5.85 (1H, d, J=9.2 Hz),5.74 (1H, d, J=17.8 Hz), 5.53 (1H, d, J=17.8 Hz), 4.68-4.42 (5H, m),3.14 (2H, t, J=6.4 Hz), 2.97 (1H, dd, J=4.0, 17.4 Hz), 2.67 (1H, dd,J=5.0,17.4 Hz), 1.40 (9H, s).

EXAMPLE 14(42)N-(2-(pyridin-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.22 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 8.55 (1H, d,J=5.0 Hz), 7.68-7.60 (1H, m), 7.39-7.12 (5H, m), 5.82 (1H, d, J=8.0 Hz),5.69 (1H, d, J=18.8 Hz), 5.53 (1H, d, J=18.8 Hz), 4.75-4.45 (3H, m),4.40-4.20 (2H, m), 3.17 (2H, t, J=6.6 Hz), 3.13-3.02 (1H, m), 2.75 (1H,dd, J=4.8, 17.4 Hz), 1.41 (9H, s).

EXAMPLE 14(43)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.79 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.38-7.06 (5H,m), 6.73 (2H, s), 6.57 (1H, d, J=8.4 Hz), 5.63 (1H, d, J=17.8 Hz), 5.43(1H, d, J=17.8 Hz), 4.92-4.72 (1H, m), 3.36-3.12 (2H, m), 3.12-3.09 (3H,m), 2.99 (6H, s), 2.65 (1H, dd, J=17.4 and 4.6 Hz), 1.42 (9H, s).

EXAMPLE 14(44)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.67 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.41-7.09 (5H,m), 6.70 (2H, s), 6.63 (1H, d, J=8.6 Hz), 5.54 (1H, d, J=18.4 Hz), 5.34(1H, d, J=18.4 Hz), 4.98-4.74 (1H, m), 3.38-3.15 (2H, m), 3.15-2.80 (3H,m), 2.99 (6H, s), 2.69 (1H, dd, J=17.6 and 4.8 Hz), 1.44 (9H, s).

EXAMPLE 14(45)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.46 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.49 (1H, d,J=8.7 Hz), 7.39 (1H, d; J=8.7 Hz), 7.15 (2H, d, J=8.7 Hz), 6.83 (2H, d,J=8.7 Hz), 5.82 (1H, d, J=9.2 Hz), 5.73-5.44 (2H, m), 4.58 (1H, m),4.48-4.22 (2H, m), 3.74 (3H, s), 3.00 (1H, dd, J=17 Hz, 5 Hz), 2.90 (2H,t, J=6.9 Hz), 2.66 (1H, dd, J=17 Hz, 4.7 Hz), 1.42 (9H, s).

EXAMPLE 14(46)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.38 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.51 (1H, d,J=8.8 Hz), 7.39 (1H, d, J=8.8 Hz), 7.16 (2H, d, J=8.6 Hz), 6.85 (2H, d,J=8.6 Hz), 5.86 (1H, d, J=9.4 Hz), 5.66-5.38 (2H, m), 4.63 (1H, m),4.51-4.26 (2H, m), 3.75 (3H, s), 3.08 (1H, dd, J=18 Hz, 4.0 Hz), 2.93(2H, t, 6.9 Hz), 2.70 (1H, dd, J=18 Hz, 4.6 Hz), 1.43 (9H, s).

EXAMPLE 14(47)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.21 (2H, s),7.08 (2H, d, J=8.4 Hz), 6.77 (2H, d, J=8.4 Hz), 5.74 (1H, d, J=9.5 Hz),5.65-5.36 (2H, m), 4.51 (1H, m), 4.42-4.16 (2H, m), 3.68 (3H, s),2.98-2.81 (3H, m), 2.64 (1H, dd, J=17 Hz, 4.8 Hz), 2.28 (3H, s), 1.36(9H, s).

EXAMPLE 14(48)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.33 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.27 (2H, s),7.17 (2H, d, J=8.7 Hz), 6.85 (2H, d, J=8.7 Hz), 5.88 (1H, d, J=9.2 Hz),5.65-5.36 (2H, m), 4.63 (1H, m), 4.51-4.26 (2H, m), 3.75 (3H, s), 3.06(1H, dd, J=17.6 Hz, 4.2 Hz), 2.93 (2H, t, J=7.0 Hz), 2.70 (1H, dd, J=7.6Hz, 4.7 Hz), 2.34 (3H, s), 1.44 (9H, s).

EXAMPLE 14(49)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.79 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.14 (2H, d,J=8.5 Hz), 6.83 (2H, d, J=8.5 Hz), 6.72 (2H, s), 5.81 (1H, d, J=9 Hz),5.62-5.42 (2H, m), 4.57 (1H, m), 4.47-4.21 (2H, m), 3.74 (3H, s), 2.99(6H, s), 2.90 (3H, m), 2.66 (1H, dd, J=17 Hz, 4.5 Hz), 1.42 (9H, s).

EXAMPLE 14(50)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.69 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.16 (2H, d,J=8.4 Hz), 6.85 (2H, d, J=8.4 Hz), 6.70 (2H, s), 5.88 (1H, d, J=9 Hz),5.61-5.32 (2H, m), 4.62 (1H, m), 4.50-4.26 (2H, m), 3.75 (3H, s),3.09-2.90 (3H, m), 2.99 (6H, s), 2.70 (1H, dd, J=17 Hz, 4.4 Hz), 1.44(9H, s).

EXAMPLE 14(51)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.61 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.13 (2H, d,J=8.6 Hz), 6.81 (2H, d, J=8.6 Hz), 6.49 (2H, s), 5.81 (1H, d, J=9.0 Hz),5.61 (1H, d, J=17.9 Hz), 5.41 (I H, d, J=17.9 Hz), 4.63-4.15 (3H, m),3.73 (3H, s), 3.05-2.80 (3H, m), 2.96 (6H, s), 2.64 (1H, dd, J=17.3, 4.7Hz), 2.44(6H, s), 1.42 (9H, s).

EXAMPLE 14(52)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.45 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 67.16 (2H, d,J=8.7 Hz), 6.84 (2H, d, J=8.7 Hz), 6.49 (2H, s), 5.84 (1H, d, J=9.2 Hz),5.41 (1H, d, J=18.4 Hz), 5.20 (1H, d, J=8.4 Hz), 4.63-4.20 (3H, m), 3.73(3H, s), 3.05-2.85 (3H, m), 2.97 (6H, s), 2.65 (1H, dd, J=17.5, 4.8 Hz),2.38 (6H, s), 1.43 (9H, s).

EXAMPLE 14(53)N-(4-(4-methoxyphenyl)butyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.49 (1H, d,J=8.8Hz), 7.39 (1H, d, J=8.8Hz), 7.09 (2H, d, J=8.5 Hz), 6.82 (2H, d,J=8.5 Hz), 5.80 (1H, d, J=17.9 Hz), 5.80 (1H, m), 5.61 (1H, d, J=17.9Hz), 4.64 (1H, m), 4.14 (2H, m), 3.78 (3H, s), 3.01 (1H, dd, J=17.5 Hz,4.4 Hz), 2.69 (1H, dd, J=17.5 Hz, 4.8 Hz), 2.59 (2H, m), 1.65 (4H, m),1.42 (9H, s).

EXAMPLE 14(54)N-(4-(4-methoxyphenyl)butyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.34 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 57.52 (1H, d,J=8.8 Hz), 7.40 (1H, d, J=8.8 Hz), 7.10 (2H, d, J=8.4 Hz), 6.83 (2H, d,J=8.4 Hz), 5.88 (1H, d, J=8.4 Hz), 5.73 (1H, d, J=8.4 Hz), 5.56 (1H, d,J=18.9 Hz), 4.68 (1H, m), 4.19 (2H, m), 3.78 (3H, s), 3.10 (1H, dd,J=17.6 Hz, 4.4 Hz), 2.74 (1H, dd,J=17.6 Hz, 4.8 Hz), 2.61 (2H, m), 1.69(4H, m), 1.45 (9H, s).

EXAMPLE 14(55)N-(4-(4-methoxyphenyl)butyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.35 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.09 (2H, d,J=8.6 Hz), 6.82 (2H, d, J=8.6 Hz), 6.72 (2H, s), 5.81 (1H, m), 5.75 (1H,d, J=17.8 Hz), 5.57 (1H, d, J=17.8 Hz), 4.60 (1H, m), 4.14 (2H, m), 3.78(3H, s), 2.99 (6H, s), 2.95 (1H, m), 2.74-2.66 (1H, m), 2.59 (2H, m),1.67 (4H, m), 1.42 (9H, s).

EXAMPLE 14(56)N-(4-(4-methoxyphenyl)butyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.24 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 67.10 (2H, d,J=8.6 Hz), 6.82 (2H, d, J=8.6 Hz), 6.70 (2H, s), 5.88 (1H, m), 5.66 (1H,d, J=18.4 Hz), 5.47 (1H, d, J=8.4 Hz), 4.65 (1h, m), 4.14 (2H, m), 3.78(3H, s), 3.05 (1H, dd, J=17.2 Hz, 4.4 Hz), 2.99 (6H, s), 2.72 (1H, dd,J=17.2 Hz, 4.8 Hz), 2.59 (2H, m), 1.69 (4H, m), 1.44 (9H, s).

EXAMPLE 14(57)N-(2-(4-methylthiazol-5-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.60 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 8.59 (1H, s),7.48-7.28 (3H, m), 5.99 (1H, m), 5.76 (1H, d, J=17.8 Hz), 5.59 (1H, d,J=17.8 Hz), 4.64 (1H, m), 4.29 (2H, t, J=6.6 Hz), 3.12 (2H, t, J=6.6Hz), 2.97 (1H, dd, J=18 Hz, 4.4 Hz), 2.71 (1H, dd, J=18 Hz, 5.0 Hz),2.41 (3H, s), 1.42 (9H, s).

EXAMPLE 14(58)N-(2-(4-methylthiazol-5-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.51 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 8.60 (1H, s),7.48-7.27 (3H, m), 5.99 (1H, m), 5.69 (1H, d, J=8.2 Hz), 5.52 (1H, d,J=18.2 Hz), 4.66 (1H, m), 4.36 (2H, t, J=6.2 Hz), 3.16 (2H, t, J=6.2Hz), 3.08 (1H, dd, J=17.6 Hz, 4.4 Hz), 2.74 (1H, dd, J=17.6 Hz, 5.0 Hz),2.44 (3H, s), 1.45 (9H, s).

EXAMPLE 14(59)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.49 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.47-7.43 (2H,m), 7.34-7.14 (6H, m), 6.57 (1H, d, J=8.8 Hz), 5.66 (1H, d, J=17.8 Hz),5.44 (1H, d, J=17.8 Hz), 4.82 (1H, m), 3.29-3.20 (2H, m), 3.04-2.89 (3H,m), 2.65 (1H, dd, J=17.4 Hz, 4.6 Hz), 1.42 (9H, s).

EXAMPLE 14(60)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.35 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.48-7.43 (2H,m), 7.36-7.18 (6H, m), 6.64 (1H, d, J=8.8 Hz), 5.60 (1H, d, J=18.6 Hz),5.41 (1H, d, J=18.6 Hz), 4.89 (1H, m), 3.31-3.24 (2H, m), 3.12-2.93 (3H,m), 2.70 (1H, dd, J=17 Hz, 4.6 Hz), 1.45 (9H, s).

EXAMPLE 14(61)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(4-(pyrrolidin-1-ylmethyl)phenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.45 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.62 (2H, d, J=8.8Hz), 7.55 (2H, d, J=8.8 Hz), 7.38-7.10 (5H, m), 6.79 (1H, d, J=8.4 Hz),5.78 (1H, d, J=17.7 Hz), 5.57 (1H, d, J=17.7 Hz), 4.98-4.83 (1H, m),4.13 (2H, s), 3.30-2.63 (10H, m), 2.23-2.00 (4H, m), 1.44 (9H, s).

EXAMPLE 14(62)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(4-(pyrrolidin-1-ylmethyl)phenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.62 (2H, d, J=8.3Hz), 7.51 (2H, d, J=8.3 Hz), 7.41-7.10 (6H, m), 5.68 (1H, d, J=18.6 Hz),5.45 (1H, d, J=18.6 Hz), 4.98-4.80 (1H, m), 4.30 (1H, d, J=12.7 Hz),3.94 (1H, d, J=1-2.7 Hz), 3.33-2.66 (10H, m), 2.3-2.00 (4H, m), 1.41(9H, s).

EXAMPLE 14(63)N-(2-(4-methylthiazol-5-yl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.67 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 8.58 (1H, s),7.47-7.41 (2H, m), 7.34-7.24 (2H, m), 6.69 (1H, d, J=8.8 Hz), 5.74 (1H,d, J=17.6 Hz), 5.56 (1H, d, J=17.6 Hz), 4.86 (1H, m), 3.14 (4H, m), 2.98(1H, dd, J=17.6 Hz, 4.4 Hz), 2.69 (1H, dd, J=17.6 Hz, 4.8 Hz), 2.43 (1H,s), 1.43 (9H, s).

EXAMPLE 14(64)N-(2-(4-methylthiazol-5-yl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.58 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 8.59 (1H, s),7.48-7.43 (2H, m), 7.37-7.27 (2H, m), 6.83 (1H, d, J=8.8 Hz), 5.67 (1H,d, J=18.6 Hz), 5.50 (1H, d, J=18.6 Hz), 4.92 (1H, m), 3.18 (4H, m), 3.05(1H, dd, J=17.4 Hz, 4.6 Hz), 2.76 (1H, dd, J=17.4 Hz, 5.0 Hz), 2.44 (1H,s), 1.43 (9H, s).

EXAMPLE 14(65)N-(butylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.68 (hexane:ethyl acelate=2:1); NMR (CDCl₃): δ 7.37-7.16 (3H,m), 6.50 (1H, d, J=9.0 Hz), 5.67 (1H, d, J=17.8 Hz), 5.47 (1H, d, J=17.8Hz), 4.76 (1H, m), 2.89 (1H, dd, J=17.4 Hz, 4.8 Hz), 2.86 (2H, t, J=7.2Hz), 2.59 (1H, dd, J=17.4 Hz, 4.8 Hz), 1.57 (2H, m), 1.34 (2H, m), 1.33(9H, s), 0.83 (3H, t, J=7.2 Hz).

EXAMPLE 14(66)N-(butylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.39-7.18 (3H,m), 6.59 (1H, d, J=8.6 Hz), 5.61 (1H, d, J=18.2 Hz), 5.44 (1H, d, J=18.2Hz), 4.85 (1H, m), 3.00 (1H, dd, J=17.4 Hz, 4.6 Hz), 2.93 (2H, t, J=7.3Hz), 2.66 (1H, dd, J=17.4 Hz, 4.8 Hz), 1.58 (2H, m), 1.41 (2H, m), 1.37(9H, s), 0.86 (3H, t, J=7.3 Hz).

EXAMPLE 14(67)N-(2-(4-methoxyphenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid-t-butylester

TLC:Rf 0.39 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.48-7.43 (2H,m), 7.34-7.29 (1H, m), 7.14 (2H, d, J=8.6 Hz), 6.83 (2H, d, J=8.6 Hz),6.58 (1H, d, J=8.6 Hz), 5.70 (1H, d, J=17.8 Hz), 5.49 (1H, d, J=17.8Hz), 4.85 (1H, m), 3.75 (3H, s), 3.23-3.09 (2H, m), 3.04-2.86 (3H, m),2.66 (1H, dd, J=18 Hz, 4.6 Hz), 1.42 (9H, s).

EXAMPLE 14(68)N-(2-(4-methoxyphenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.27 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.48-7.43 (2H,m), 7.36-7.28 (1H, m), 7.16 (2H, d, J=8.8 Hz), 6.84 (2H, d, J=8.8 Hz),6.13 (1H, d, J=8.8 Hz), 5.63 (1H, d, J=18.4 Hz), 5.45 (1H, d, J=18.4Hz), 4.90 (1H, m), 3.76 (3H, s), 3.24 (2H, m), 3.07 (1H, dd, J=18 Hz,4.4 Hz), 2.92 (2H, m), 2.71 (1H, dd, J=18 Hz, 4.6 Hz), 1.45 (9H, s).

EXAMPLE 14(69)N-(3-(pyrimidin-2-yl)propyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.51 (chloroform:t-butanol=20:1); NMR (CDCl₃): δ 8.66 (2H, d,J=5.0 Hz), 7.44 (2H, d, J=6.5 Hz), 7.30 (1H, m), 7.14 (1H, t, J=5.0 Hz),5.92-5.56 (3H, m), 4.60 (1H, m), 4.22 (2H, t, J=6.0 Hz), 3.13-2.85 (3H,m), 2.69 (1H, dd, J=17.0, 5.0 Hz), 2.22 (2H, m), 1.44 (9H, s).

EXAMPLE 14(70)N-(3-(pyrimidin-2-yl)propyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.45 (chloroform:t-butanol=20:1); NMR (CDCl₃): δ 8.78 (2H, d,J=5.0 Hz), 7.45 (2H, d, J=7.0 Hz), 7.32 (1H, m), 7.15 (1H, t, J=5.0 Hz),5.93 (1H, d, J=8.5 Hz), 5.75 and 5.59 (each 1H, each d, J=18.0 Hz), 4.66(1H, m), 4.28 (2H, t, J=6.5 Hz), 3.10 (3H, m), 2.74 (1H, dd, J=17.0, 5.0Hz), 2.25 (2H, m), 1.46 (9H, s).

EXAMPLE 14(71)N-(2-(4-acetylaminophenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.66 (hexane:ethyl acetate=3:7); NMR (CDCl₃): δ 7.53-7.08 (8H,m), 6.58 (1H, d, J=8.6 Hz), 5.64 (1H, d, J=17.7 Hz), 5.44 (1H, d, J=17.7Hz), 4.86-4.73 (1H, m), 3.30-2.55 (6H, m), 2.14 (3H, s), 1.42 (9H, s).

EXAMPLE 14(72)N-(2-(4-acetylaminophenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.57 (hexane:ethyl acetate=3:7); NMR (CDCl₃): δ 7.54 (1H, s),7.50-7.23 (5H, m), 7.17 (2H, d, J=8.4 Hz), 6.82 (1H, d, J=8.4 Hz), 5.59(1H, d, J=18.5 Hz), 5.38 (1H, d, J=18.5 Hz), 4.95-4.81 (1H, m),3.40-2.62 (6H, m), 2.10 (3H, s), 1.44 (9H, s).

EXAMPLE 14(73)N-butyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.48 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.47-7.43 (2H,m), 7.34-7.27 (1H, m), 5.80 (1H, d, J=18.0 Hz), 5.79 (1H, m), 5.61 (1H,d, J=18.0 Hz), 4.62 (1H, m), 4.14 (2H, m), 2.99 (1H, dd, J=17.4 Hz, 4.6Hz), 2.70 (1H, dd, J=17.4 Hz, 5.0 Hz), 1.64 (2H, m), 1.43 (9H, s), 1.37(2H, m), 0.94 (3H, t, J=7.4 Hz).

EXAMPLE 14(74)N-butyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.38 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.48-7.43 (2H,m), 7.36-7.27 (1H, m), 5.89 (1H, d, J=8.8 Hz), 5.73 (1H, d, J=18.4 Hz),5.55 (1H, d, J=18.4 Hz), 4.68 (1H, m), 4.20 (2H, m), 3.08 (1H, dd,J=17.6 Hz, 4.4 Hz), 2.75 (1H, dd, J=17.6 Hz, 5.0 Hz), 1.63 (2H, m), 1.45(9H, s), 1.41 (2H, m), 0.96 (3H, t, J=7.2 Hz).

EXAMPLE 14(75)N-(propylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.57 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.50-7.21 (3H,m), 6.59 (1H, d, J=8.6 Hz), 5.77 (1H, d, J=17.6 Hz), 5.57 (1H, d, J=17.6Hz), 4.92-4.78 (1H, m), 3.08-2.87 (3H, m), 2.69 (1H, dd, 17.5, 4.7 Hz),1.80-1.55 (2H, m), 1.43 (9H, s), 1.00 (3H, t, J=7.3 Hz).

EXAMPLE 14(76)N-(propylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.50-7.25 (3H,m), 6.65 (1H, d, J=8.8 Hz), 5.69 (1H, d, J=18.2 Hz), 5.51 (1H, d, J=18.2Hz), 5.00-4.85 (1H, m), 3.16-2.93 (3H, m), 2.74 (1H, dd, 17.5, 4.9 Hz),1.81-1.57 (2H, m), 1.45 (9H, s), 1.02 (3H, t, J=7.3 Hz).

EXAMPLE 14(77)N-(isopropylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.34 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.50-7.23 (3H,m), 6.52 (1H, d, J=8.8 Hz), 5.78 (1H, d, J=17.7 Hz), 5.58 (1H, d, J=17.7Hz), 4.92-4.78 (1H, m), 3.69 (1H, sep, J=6.8 Hz), 2.99 (1H, dd, 17.5,4.4 Hz), 2.69 (1H, dd, 17.5, 4.7 Hz), 1.43 (9H, s), 1.37 (6H, t, J=6.8Hz).

EXAMPLE 14(78)N-(isopropylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.12 (hexane:ethyl acetate=3:2); NMR (CDCl₃): δ 7.50-7.25 (3H,m), 6.58 (1H, d, J=8.8 Hz), 5.69 (1H, d, J=18.6 Hz), 5.52 (1H, d, J=18.6Hz), 5.00-4.83 (1H, m), 3.73 (1H, sep, J=7.0 Hz), 3.08 (1H, dd, 17.5,4.6 Hz), 2.73 (1H, dd, 17.5, 4.9 Hz), 1.45 (9H, s), 1.40 (6H, t, J=6.8Hz).

EXAMPLE 14(79)N-(2-methoxyethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.45 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.47-7.43 (2H,m), 7.34-7.26 (1H, m), 5.96 (1H, d, J=9.2 Hz), 5.81 (1H, d, J=17.8 Hz),5.62 (1H, d, J=17.8 Hz), 4.60 (1H, m), 4.30 (2H, m), 3.61 (2H, t, J=4.4Hz), 3.40 (3H, s), 3.02 (1H, dd, J=17.4 Hz, 4.2 Hz 2.69 (1H, dd, J=17.4Hz, 4.6 Hz), 1.42 (9H, s).

EXAMPLE 14(80)N-(2-methoxyethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.40 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.48-7.43 (2H,m), 7.37-7.28 (1H, m), 6.06 (1H, d, J=7.6 Hz), 5.75 (1H, d, J=18.0 Hz),5.57 (1H, d, J=18.0 Hz), 4.68 (1H, m), 4.35 (2H, m), 3.65 (2H, t, J=4.4Hz), 3.42 (3H, s), 3.12 (1H, dd, J=17.4 Hz, 4.4 Hz), 2.74 (1H, dd,J=17.4 Hz, 4.8 Hz), 1.44 (9H, s).

EXAMPLE 14(81)N-(2-cyclohexylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.53 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.50-7.28 (3H,m), 5.80 (1H, d, J=17.8 Hz), 5.79 (1H, d, J=9.0 Hz), 5.61 (1H, d, J=17.8Hz), 4.70-4.55 (1H, m), 4.17 (2H, t, J=6.8 Hz), 2.99 (1H, dd, 17.4, 4.4Hz), 2.70 (1H, dd, 17.4, 4.8 Hz), 1.80-1.46 (7H, m), 1.43 (9H, s),1.38-0.80 (6H, m).

EXAMPLE 14(82)N-(2-cyclohexylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.30 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.50-7.28 (3H,m), 5.86 (1H, d, J=9.0 Hz), 5.73 (1H, d, J=18.5 Hz), 5.55 (1H, d, J=18.5Hz), 4.75-4.60 (1H, m), 4.22 (2H, t, J=6.8 Hz), 3.08 (1H, dd, 17.5, 4.5Hz), 2.75 (1H, dd, 17.5, 4.8 Hz), 1.80-1.50 (7H, m), 1.45 (9H, s),1.40-0.80 (6H, m).

EXAMPLE 14(83)N-cyclohexylmethyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.50-7.28 (3H,m), 5.81 (1H, d, J=9.4 Hz), 5.80 (1H, d, J=17.8 Hz), 5.61 (1H, d, J=17.8Hz), 4.70-4.55 (1H, m), 3.94 (2H, d, J=6.4 Hz), 2.99 (1H, dd, 17.4, 4.6Hz), 2.70 (1H, dd, 17.4, 4.7 Hz), 1.80-1.50 (5H, m), 1.43 (9H, s),1.40-0.80 (6H, m).

EXAMPLE 14(84)N-cyclohexylmethyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.29 (hexane:ethyl acetate=7:3); NMR (CDCl₃): δ 7.50-7.28 (3H,m), 5.87 (1H, d, J=8.8 Hz), 5.73 (1H, d, J=18.4 Hz), 5.55 (1H, d, J=18.4Hz), 4.75-4.60 (1H, m), 4.30-3.90 (2H, m), 3.08 (1H, dd, 17.3, 4.6 Hz),2.75 (1H, dd, 17.3, 4.8 Hz), 1.85-1.50 (5H, m), 1.45 (9H, s), 1.40-0.80(6H, m).

EXAMPLE 14(85)N-(2-phenylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.46 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.44 (2H, d,J=6.8 Hz), 7.33-7.15 (6H, m), 5.86 (1H, d, J=8.8 Hz), 5.64 (1H, d,J=17.8 Hz), 5.34 (1H, d, J=17.8 Hz), 4.58 (1H, m), 4.48-4.25 (2H, m),2.99-2.87 (3H, m), 2.66 (1H, dd, J=17.6 Hz, 5.0 Hz), 1.41 (9, s).

EXAMPLE 14(86)N-(2-phenylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.34 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.47-7.43 (2H,m), 7.36-7.19 (6H, m), 5.91 (1H, d, J=9 Hz), 5.59 (1H, d, J=19.2 Hz),5.39 (1H, d, J=19.2 Hz), 4.63 (1H, m), 4.50-4.30 (2H, m), 3.11-2.96 (3H,m), 2.70 (1H, dd, J=17 Hz, 4.6 Hz), 1.44 (9H, s).

EXAMPLE 14(87)N-butyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-acetylaminophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:3); NMR (CDCl₃): δ 8.47 (1H, s),7.58 (2H, s), 5.90-5.75 (1H, m), 5.88 (1H, d, J=17.7 Hz), 5.69 (1H, d,J=17.7 Hz), 4.73-4.58 (1H, m), 4.14 (2H, t, J=6.9 Hz), 3.01 (1H, dd,17.4, 4.6 Hz), 2.73 (1H, dd, 17.4, 4.9 Hz), 2.07 (3H, s), 1.70-1.30 (4H,m), 1.43 (9H, s), 0.95 (3H, t, J=7.2 Hz).

EXAMPLE 14(88)N-butyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-acetylaminophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.35 (hexane:ethyl:acetate=2:3); NMR (CDCl₃): δ 9.44 (1H, s),7.53 (2H, s), 5.83 (1H, d, J=9.2 Hz), 5.75 (1H, d, J=18.4 Hz), 5.61 (1H,d, J=18.4 Hz), 4.75-4.62 (1H, m), 4.19 (2H, t, J=6.7 Hz), 3.13 (1H, dd,17.5, 4.5 Hz), 2.77 (1H, dd, 17.5, 4.7 Hz), 2.08 (3H, s), 1.75-1.30 (4H,m), 1.45 (9H, s), 0.96 (3H, t, J=7.3 Hz).

EXAMPLE 14(89)N-(2-(4-cyanophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.20 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.62 (2H, d,J=8.0 Hz), 7.48-7.24 (5H, m), 5.83 (1H, d, J=8.0 Hz), 5.72 and 5.56(each 1H, each d, J=18.0 Hz), 4.58 (1H, m), 4.36 (2H, t, J=6.5 Hz),3.09-2.86 (3H, m), 2.69 (1H, dd, J=17.5, 5.0 Hz), 1.41 (9H, s).

EXAMPLE 14(90)N-(2-(4-cyanophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.13 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.62 (2H, d,J=8.0 Hz), 7.49-7.23 (5H, m), 5.90 (1H, d, J=8.5 Hz), 5.66 and 5.51(each 1H, each d, J=17.5 Hz), 4.64 (1H, m), 4.41 (2H, t, J=6.5 Hz),3.13-2.96 (3H, m), 2.72 (1H, dd, J=17.0, 5.0 Hz), 1.44 (9H, s).

EXAMPLE 14(91)N-(2-(4-cyanophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

HPTLC:Rf 0:21 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.62 (2H, d,J=8.0 Hz), 7.33 (2H, d, J=8.0 Hz), 7.27 (2H, S), 5.83 (1H, d, J=8.0 Hz),5.70 and 5.55 (each 1H, each d, J=17.5 Hz), 4.58 (1H, m), 4.36 (2H, t,J=6.5 Hz), 3.08-2.85 (3H, m), 2.67 (1H, dd, J=17.0, 5.0 Hz), 2.34 (3H,s), 1.41 (9H, s).

EXAMPLE 14(92)N-(2-(4-cyanophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.15 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.62 (2H, d,J=8.0 Hz), 7.36 (2H, d, J=8.0 Hz), 7.28 (2H, s), 5.90 (1H, d, J=7.5 Hz),5.65 and 5.49 (each 1H, each d, J=18.5 Hz), 4.65 (1H, m), 4.40 (2H, t,J=6.5 Hz), 3.14-2.93 (3H, m), 2.72 (1H, dd, J=17.0, 5.0 Hz), 2.35 (3H,s), 1.44 (9H, s).

EXAMPLE 14(93)N-(2-methoxyethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.65 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 67.47-7.43 (2H,m), 7.28 (1H, dd, J=6.8 Hz, 2.2 Hz), 6.81 (1H, d, J=8.6 Hz), 5.78 (1H,d, J=18.0 Hz), 5.58 (1H, d, J=18.0 Hz), 4.87 (1H, m), 3.59 (2H, t, J=6.2Hz), 3.36 (3H, s), 3.17 (2H, t, J=6.2 Hz), 2.98 (1H, dd, J=17.4 Hz, 4.4Hz), 2.70 (1H, dd, J=17.4 Hz, 4.4 Hz), 1.43 (9H, s).

EXAMPLE 14(94)N-(2-methoxyethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.52 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.48-7.43 (2H,m), 7.30 (1H, dd, J=9.2 Hz, 2.6 Hz), 6.89 (1H, d, J=8.8 Hz), 5.70 (1H,d, J=18.6 Hz), 5.52 (1H, d, J=18.6 Hz), 4.91 (1H, m), 3.63 (2H, t, J=6.0Hz), 3.40 (3H, s), 3.18 (2H, t, J=6.0 Hz), 3.08 (1H, dd, J=17.6 Hz, 4.4Hz), 2.75 (1H, dd, J=17.6 Hz, 4.8 Hz), 1.45 (9H, s).

EXAMPLE 14(95)N-(2-(2-methoxyethyloxy)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.54 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 7.47-7.43 (2H,m), 7.34-7.29 (1H, m), 6.00 (1H, d, J=8.8 Hz), 5.83 (1H, d, J=17.6 Hz),5.62 (1H, d, J=17.6 Hz), 4.62 (1H, m), 4.30 (2H, m), 3.72 (2H, t, J=4.8Hz), 3.64 (2H, m), 3.56 (2H, m), 3.36 (3H, s), 3.00 (1H, dd, J=17.6 Hz,4.6 Hz), 2.70 (1H, dd, J=17.6 Hz, 5.0 Hz), 1.42(9H, s).

EXAMPLE 14(96)N-(2-(2-methoxyethyloxy)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.42 (hexane:ethyl acetate=1:2); NMR (CDCl₃): δ 7.48-7.43 (2H,m), 7.36-7.27 (1H, m), 6.05 (1H, d, J=9.4 Hz), 5.75 (1H, d, J=18.2 Hz),5.56 (1H, d, J=18.2 Hz), 4.66 (1H, m), 4.35 (2H, m), 3.76 (2H, t, J=4.6Hz), 3.67 (2H, m), 3.57 (2H, m), 3.38 (3H, s), 3.13 (1H, dd, J=17.4 Hz,4.0 Hz), 2.74 (1H, dd, J=17.4 Hz, 5.0 Hz), 1.45 (9H, s).

EXAMPLE 14(97)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2-chlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.55 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.48-7.43 (2H,m), 7.33-7.15 (7H, m), 6.60 (1H, d, J=8.8 Hz), 5.73 (1H, d, J=17.8 Hz),5.53 (1H, d, J=17.8 Hz), 4.86 (1H, m), 3.24 (2H, m), 3.00 (1H, dd,J=17.4 Hz, 4.4 Hz), 2.97 (2H, m), 2.67 (1H, dd, J=17.4 Hz, 4.8 Hz), 1.43(9H, s).

EXAMPLE 14(98)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2-chlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.40 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.57-7.43 (2H,m), 7.33-7.17 (7H, m), 6.62 (1H, d, J=8.4 Hz), 5.78 (1H, d, J=18.6 Hz),5.39 (1H, d, J=18.6 Hz), 4.87 (1H, m), 3.26 (2H, m), 3.03 (1H, dd,J=17.4 Hz, 4.4 Hz), 2.97 (2H, m), 2.68 (1H, dd, J=17.4 Hz, 4.8 Hz), 1.43(9H, s).

EXAMPLE 14(99)N-(2-acetylaminoethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.69 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.50-7.28 (3H, m),6.89 (1H, d, J=8.0 Hz), 6.25-6.07 (1H, m), 5.76 (1H, d, J=17.7 Hz), 5.60(1H, d, J=17.7 Hz), 4.93-4.75 (1H, m), 3.48 (2H, q, J=6.2 Hz), 3.08 (2H,t, J=6.2 Hz), 2.95 (1H, dd, 17.4, 4.9 Hz), 2.73 (1H, dd, 17.4, 5.0 Hz),1.97 (3H, s), 1.43 (9H, s).

EXAMPLE 14(100)N-(2-acetylaminoethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.65 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.50-7.28 (3H, m),6.93 (1H, d, J=8.8 Hz), 6.20-6.06 (1H, m), 5.70 (1H, d, J=18.4 Hz), 5.53(1H, d, J=18.4 Hz), 5.00-4.85 (1H, m), 3.52 (2H, q, J=6.4 Hz), 3.12 (2H,t, J=6.4 Hz), 3.06 (1H, dd, 17.4, 4.6 Hz), 2.75 (1H, dd, 17.4, 5.2 Hz),1.99 (3H, s), 1.45 (9H, s).

EXAMPLE 14(101)N-(2-acetylaminoethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.50 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.48-7.43 (2H, m),7.35-7.32 (1H, m), 6.16 (1H, brs), 5.01 (1H, d, J=8.6 Hz), 5.78 (1H, d,J=17.6 Hz), 5.63 (1H, d, J=17.6 Hz), 4.60 (1H, m), 4.20 (2H, m), 3.50(2H, m), 3.00-2.85 (1H, m), 2.75 (1H, dd, J=17.6 Hz, 5.0 Hz), 1.98 (3H,s), 1.43 (9H, s).

EXAMPLE 14(102)N-(2-acetylaminoethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.48 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.49-7.44 (2H, m),7.37-7.33 (1H, m), 6.06 (2H, m), 5.74 (1H, d, J=18.6 Hz), 5.55 (1H, d,J=18.6 Hz), 4.68 (1H, m), 4.26 (2H, m), 3.54 (2H, m), 3.06 (1H, dd,J=17.6 Hz, 4.4 Hz), 2.77 (1H, dd, J=17.6 Hz, 5.0 Hz), 2.00 (3H, s), 1.45(9H, s).

EXAMPLE 14(103)N-(2-(2-methoxyethyloxy)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.49 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.50-7.28 (3H,m), 6.76 (1H, d, J=8.4 Hz), 5.77 (1H, d, J=17.8 Hz), 5.58 (1H, d, J=17.8Hz), 4.90-4.75 (1H, m), 3.80-3.50 (6H, m), 3.37 (3H, s), 3.18 (2H, t,J=6.1 Hz), 2.98 (1H, dd, 17.4, 4.5 Hz), 2.69 (1H, dd, 17.4, 4.9 Hz),1.43 (9H, s).

EXAMPLE 14(104)N-(2-(2-methoxyethyloxy)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.39 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.50-7.28 (3H,m), 6.83 (1H, d, J=9.0 Hz), 5.69 (1H, d, J=18.4 Hz), 5.51 (1H, d, J=18.4Hz), 5.00-4.85 (1H, m), 3.80-3.50 (6H, m), 3.38 (3H, s), 3.23 (2H, t,J=6.3 Hz), 3.07 (1H, dd, 17.5, 4.6 Hz), 2.75 (1H, dd, 17.5, 4.9 Hz),1.45 (9H, s).

EXAMPLE 14(105)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(phenylthio)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.57 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.59-7.55 (2H,m), 7.37-7.15 (8H, m), 6.62 (1H, d, J=8.8 Hz), 5.71 (1H, d, J=17.8 Hz),5.50 (1H, d, J=17.8 Hz), 4.85 (1H, m), 3.32 (2H, m), 3.05-2.90 (3H, m),2.67 (1H, dd, J=7.4 Hz, 4.8 Hz), 1.43 (9H, s).

EXAMPLE 14(106)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(phenylthio)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.57-7.51 (2H,m), 7.39-7.15 (8H, m), 6.63 (1H, d, J=8.6 Hz), 5.49 (1H, d, J=18.4 Hz),5.30 (1H, d, J=18.4 Hz), 4.82 (1H, m), 3.27 (2H, m), 3.07-2.91 (3H, m),2.67 (1H, dd, J=17.6 Hz, 4.8 Hz), 1.44 (9H, s).

EXAMPLE 15(1)-15(106)

By the same procedure as provided in example 6(1), and if necessary, byknown methods converted to accommodate the corresponding salts, usingthe compound prepared in example 14(1)-14(106), compounds of the presentinvention having the following physical data were obtained.

EXAMPLE 15(1)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.61 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.65-12.30 (1H, br), 8.96-8.82 (1H, m), 7.52 (2H, d, J=7.5 Hz),7.45-7.13 (6H, m), 6.05-5.70 (2H, m), 4.87-4.72 (1H, m), 4.52 (2H, s),4.11 (2H, s), 2.90-2.55 (2H, m).

EXAMPLE 15(2)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.19 (chloroform:methanol acetic acid=18:1:1); NMR (DMSO-d₆): δ9.05-8.95 (1H, m), 7.54 (2H, d, J=7.5 Hz), 7.46-7.10 (6H, m), 6.00-5.75(2H, m), 4.92-4.75 (1H, m), 4.33 (2H, s), 4.11 (2H, s), 2.88-2.70 (2H,m).

EXAMPLE 15(3)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.58 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.88 (1H, d, J=6.2 Hz), 7.69-7.50 (3H, m), 7.33-7.12 (5H, m), 5.89 (2H,brs), 4.85-4.73 (1H, m), 4.10 (2H, s), 2.80 (1H, dd, J=6.0, 17 Hz), 2.64(1H, dd, J=7.2, 17 Hz).

EXAMPLE 15(4)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.36 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.99 (1H, d, J=6.4 Hz), 7.70-7.52 (3H, m), 7.35-7.13 (5H, m), 5.71 (2H,brs), 4.90-4.79 (1H, m), 4.12 (2H, s), 2.92-2.68 (2H, m).

EXAMPLE 15(5)N-(2-phenylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.57 (chloroform:methanol:acetic acid=19:1:0.1); NMR (CDCl₃): δ12.70-12.10 (10H, br), 7.80 (1H, d, J=6.4 Hz), 7.55-7.15 (8H, m), 5.82(2H, s), 4.59-4.51 (3H, m), 4.23 (2H, t, J=7.0 Hz), 2.92-2.48 (4H, m).

EXAMPLE 15(6)N-(2-phenylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.52 (chloroform:methanol:acetic acid=19:1:0.1); NMR (CDCl₃): δ7.61-7.15 (9H, m), 5.90 (2H, s), 4.58-4.44 (1H, m), 4.35 (2H, s),4.30-4.16 (2H, m), 2.88 (2H, t, J=7.5 Hz), 2.63 (2H, d, J=5.6 Hz).

EXAMPLE 15(7)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.57 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ8.62 (1H, d, J=6.0 Hz), 7.50 (2H, d, J=7.2 Hz), 7.40-7.09 (6H, m), 5.88(2H, d, J=2.8 Hz), 4.74-4.63 (1H, m), 4.50 (2H, s), 3.07 (2H, t, J=7.2Hz), 2.82 (2H, t, J=7.2 Hz), 2.63-2.50 (2H, m).

EXAMPLE 15(8)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.42 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ8.89 (1H, d, J=6.4 Hz), 7.52 (2H, d, J=7.0 Hz), 7.39 (1H, dd, J=6.6, 9.0Hz), 7.25-7.13 (5H, m), 5.91 (2H, s), 4.78-4.69 (1H, m), 4.38 (2H, s),3.17-3.01 (2H, m), 2.82-2.69 (4H, m).

EXAMPLE 15(9)N-(2,6-dichlorobenzyloxy)carbonyl-3-amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.38 (chloroform:methanol:acetic acid=36:1:1); NMR (DMSO-d₆): δ8.12 (1H, d, J=7.6 Hz), 7.54-7.12 (8H, m), 5.76 (2H, s), 5.34 (2H, s),4.70-4.58 (1H, m), 4.15 (2H, s), 2.87-2.63 (2H, m).

EXAMPLE 15(10)N-(2,6-dichlorobenzyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 7.60 (1H, d,J=7.6 Hz), 7.57-7.31 (6H, m), 6.00-5.80 (2H, m), 5.30 (2H, s), 4.55-4.43(1H, m), 4.51 (2H, s), 2.60-2.54 (2H, m).

EXAMPLE 15(11)N-(3-phenylpropyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.45 (chloroform:methanol:acetic acid=90 10:1); NMR (DMSO-d₆): δ7.82 (1H, d, J=7.5 Hz), 7.51 (2H, d, J=7.6 Hz), 7.40-7.14 (6H, m),6.00-5.76 (2H, br), 4.62-4.51 (3H, m), 3.98 (2H, t, J=3.6 Hz) 2.83-2.53(4H, m), 1.94-1.80 (2H, m).

EXAMPLE 15(12)N-(3-phenylpropyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.42 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.97 (1H, d, J=7.5 Hz), 7.56-7.12 (8H, m), 5.92-5.83 (2H, br), 4.67-4.58(1H, m), 4.35 (2H, s), 4.02 (2H, t, J=6.6 Hz), 2.92-2.60 (4H, m),1.95-1.80 (2H, m).

EXAMPLE 15(13)N-(4-phenylbutyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.45 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.75 (1H, d, J=7.6 Hz), 7.52 (2H, d, J=7.2 Hz), 7.40-7.10 (6H, m), 5.87(2H, s), 4.61-4.51 (3H, m), 4.05-3.97 (2H, br), 2.77 (1H, dd, J=6.3,17.0 Hz), 2.64-2.56 (3H, m), 1.65-1.50 (4H, br).

EXAMPLE 15(14)N-(4-phenylbutyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.42 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.91 (1H, d, J=6.8 Hz), 7.54 (2H, d, J=6.6 Hz), 7.41 (1H, dd, J=6.6, 9.4Hz), 7.30-7.16 (5H, m), 5.87 (2H, s), 4.69-4.58 (1H, m), 4.35 (2H, s),4.08-4.00 (2H, br), 2.91-2. 55 (4H, m), 1.68-1.52 (4H, br).

EXAMPLE 15(15)N-(2-(thiophen-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.39 (chloroform:methanol:acetic acid=19:1:0.1); NMR (DMSO-d₆): δ7.87 (1H, d, J=7.6 Hz), 7.54-7.50 (2H, m), 7.41-7.30 (2H, m), 6.93 (2H,d, J=3.2 Hz), 5.93-5.81 (2H, br), 4.62-4.51 (3H, m), 4.18 (2H, t, J=6.6Hz), 3.11 (2H, t, J=6.6 Hz), 2.77 (1H, dd, J=6.0, 16.8 Hz), 2.58 (1H,dd, J=7.2, 16.4 Hz).

EXAMPLE 15(16)N-(2-(thiophen-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.27 (chloroform:methanol:acetic acid=19:1:0.1); NMR (DMSO-d₆): δ8.02 (1H, d, J=7.2 Hz), 7.57-7.52 (2H, m), 7.45-7.31 (2H, m), 6.94 (2H,d, J=3.8 Hz), 5.91-5.80 (2H, br), 4.70-4.60 (1H, m), 4.35 (2H, s), 4.18(2H, t, J=6.6 Hz), 3.13 (2H, t, J=6.6 Hz), 2.84 (1H, dd, J=6.6, 16.6Hz), 2.70 (1H, dd, J=6.6, 16.6 Hz).

EXAMPLE 15(17)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.51 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.78 (1H, d, J=6.8 Hz), 7.54-7.50 (2H, m), 7.37 (1H, dd, J=7.1, 9.1 Hz),7.17 (2H, d, J=8.5 Hz), 6.83 (2H, d, J=8.5 Hz), 5.90-5.85 (2H, br),4.60-4.51 (3H, m), 4.17 (2H, t, J=6.6 Hz), 3.67 (3H, s), 2.85-2.52 (4H,M).

EXAMPLE 15(18)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlcrcphenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.47 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.92 (1H, d, J=6.8 Hz), 7.56-7.52 (2H, m), 7.40 (1H, dd, J=6.8, 9.2 Hz),7.17 (2H, d, J=8.2 Hz), 6.83 (2H, d, J=8.2 Hz), 5.83 (2H, s), 4.66-4.5 6(1H, m), 4.35 (2H, s), 4.19 (2H, t, J=6.9 Hz), 3.69 (3H, s) 2.86-2.63(4H, m).

EXAMPLE 15(19)N-(2-(4-fluorophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.78 (1H, d, J=8.0 Hz), 7.51 (2H, d, J=7.6 Hz), 7.40-7.26 (3H, m), 7.08(2H, t, J=9.0 Hz), 5.82 (2H, s), 4.58-4.51 (3H, m), 4.20 (2H, t, J=6.5Hz), 2.90-2.52 (4H, m).

EXAMPLE 15(20)N-(2-(4-fluorophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.44 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.93 (1H, d, J=7.2 Hz), 7.56-7.25 (5H, m), 7.08 (2H, t, J=9.0 Hz), 5.84(2H, s), 4.66-4.57 (1H, m), 4.34 (2H, s), 4.21 (2H, t, J=6.9 Hz),2.92-2.63 (4H, m).

EXAMPLE 15(21)N-(2-(phenylmethyloxy)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.53 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ7.91 (1H, d, J=7.4 Hz), 7.54-7.50 (2H, m), 7.40-7.23 (6H, m), 5.96-5.74(2H, br), 4.61-4.50 (5H, m), 4.18 (2H, t, J=4.4 Hz), 3.62 (2H, t, J=4.4Hz), 2.78 (1H, dd, J=6.0, 17.2 Hz), 2.59 (1H, dd, J=7.0, 16.6 Hz).

EXAMPLE 15(22)N-(2-(phenylmethyloxy)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.47 (chloroform:methanol:acetic acid=90:10:1); NMR (DMSO-d₆): δ8.07 (1H, d, J=7.2 Hz), 7.56-7.23 (8H, m), 5.87 (2H, s), 4.69-4.59 (1H,m), 4.50 (2H, s), 4.35 (2H, s), 4.20 (2H, t, J=4.5 Hz), 3.64 (2H, t,J=4.5 Hz), 2.91-2.66 (2H, m).

EXAMPLE 15(23)N-(2-(4-dimethylaminophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.37 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.82 (1H, d, J=7.4 Hz), 7.52-7.32 (7H, m), 5.87 (2H, s), 4.59-4.52 (1H,m), 4.52 (2H, s), 4.27-4.19 (2H, m), 3.05 (6H, s), 2.94-2.87 (2H, m),2.94-2.61 (2H, m).

EXAMPLE 15(24)N-(2-(4-dimethylaminophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.36 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.99 (1H, d, J=7.4 Hz), 7.54-7.31 (7H, m), 5.88 (2H, s), 4.66-4.63 (1H,m), 4.36 (2H, m), 4.28-4.20 (2H, m), 3.01 (6H, s), 2.93-2.74 (4H, m).

EXAMPLE 15(25)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.51 (chloroform:methanol:water=40:16:1); NMR (DMSO-d₆): δ 8.70(1H, d, J=6 Hz), 7.82 (1H, d, J=8.8 Hz), 7.69 (1H, d, J=8.8 Hz),7.32-7.22 (5H, m), 5.94 (2H, m), 4.73 (1H, m), 4.08 (2H, s), 2.60 (2H,m).

EXAMPLE 15(26)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.43 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.83(1H, d, J=7 Hz), 7.84 (1H, d, J=8.8 Hz), 7.69 (1H, d, J=8.8 Hz),7.33-7.08 (5H, m), 5.84 (2H, m), 4.75 (1H, m), 4.09 (2H, m), 2.64 (2H,m).

EXAMPLE 15(27)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.51 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.69(1H, d, J=6.4 Hz), 7.52 (2H, s), 7.32-7.19 (5H, m), 5.92 (2H, m), 4.71(1H, m), 4.08 (2H, s), 2.56 (2H, m), 2.36 (3H, s).

EXAMPLE 15(28)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.45 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.77(1H, m), 7.51 (2H, s), 7.33-7.13 (5H, m), 5.82 (2H, m), 4.75 (1H, m),4.10 (2H, m), 2.62 (2H, m), 2.37 (3H, s).

EXAMPLE 15(29)N-(3-phenylpropylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.54 (chloroform:methanol:acetic acid=19:1:10.1); NMR (DMSO-d₆):δ 8.81 (1H, d, J=6.4 Hz), 7.51 (2H, d, J=7.2 Hz), 7.40-7.14 (6H, m),6.00-5.74 (2H, br), 4.83-4.73 (1H, m), 4.50 (2H, s), 2.87-2.56 (6H, m),1.91-1.77 (2H, m).

EXAMPLE 15(30)N-(3-phenylpropylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.41 (chloroform:methanol:acetic acid=19:1:0.1); NMR (DMSO-d₆): δ8.97 (1H, d, J=6.8 Hz), 7.55-7.36 (3H, m), 7.27-7.11 (5H, m), 5.87 (2H,s), 4.87-4.78 (1H, m), 4.34 (2H, s), 2.92-2.58 (6H, m), 1.91-1.78 (2H,m).

EXAMPLE 15(31)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.56 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.28-11.40 (1H, br), 9.03-8.77 (1H, m), 7.42-7.06 (5H, m), 6.88 (2H,s), 6.10-5.66 (2H, br), 4.90-4.68 (1H, m), 4.11 (2H, s), 3.00 (6H, s),2.92-2.53 (2H, m).

EXAMPLE 15(32)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol:acetic acid=30:1:1); NMR (DMSO-d₆): δ13.08-11.40 (1H, br), 9.13-8.86 (1H, m), 7.44-7.08 (5H, m), 6.88 (2H,s), 5.90-5.45 (2H, br), 4.95-4.71 (1H, m), 4.13 (2H, s), 3.00 (6H, s),2.93-2.62 (2H, m).

EXAMPLE 15(33)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.60 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.69(1H, m), 7.83 (1H, d, J=8.8 Hz), 7.70 (1H, d, J=8.8 Hz), 7.31-7.15 (5H,m), 5.91 (2H, m), 4.73 (1H, m), 3.06 (2H, m), 2.84 (2H, m), 2.62 (2H,m).

EXAMPLE 15(34)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.51 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₈): δ 8.87(1H, m), 7.82 (1H, d, J=8.8 Hz), 7.67 (1H, d, J=8.8 Hz), 7.27-7.14 (5H,m), 5.85 (2H, m), 4.77 (1H, m), 3.05 (2H, m), 2.83 (2H, m), 2.65 (2H,m).

EXAMPLE 15(35)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.63 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.56(1H, d, J=6 Hz), 7.49 (2H, s), 7.26-7.15 (5H, m), 5.92 (2H, m), 4.73(1H, m), 3.04 (2H, m), 2.84 (2H, m), 2.59 (2H, m), 2.35 (3H, s).

EXAMPLE 15(36)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.53 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.82(1H, d, J=6.8 Hz), 7.49 (2H, s), 7.24-7.14 (5H, m), 5.81 (2H, s), 4.77(1H, m), 3.05 (2H, m), 2.82 (2H, m), 2.66 (2H, m), 2.34 (3H, s).

EXAMPLE 15(37)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.43 (chloroform:methanol:water=50:10:1); NMR (DMSO-d₆): δ 8.96(1H, d, J=7.0 Hz), 7.34-7.18 (5H, m), 6.79 (2H, s), 5.88 (2H, m), 4.79(1H, m), 4.10 (2H, s), 2.96 (6H, s), 2.90-2.58 (2H, m), 2.38 (6H, s).

EXAMPLE 15(38) N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6,-dimethyl-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.36 (chloroform:methanol:water=50:10:1); NMR (DMSO-d₆): δ 9.05(1H, d, J=7.0 Hz), 7.38-7.16 (5H, m), 6.71 (2H, s), 5.67 (2H, s), 4.82(1H, m), 4.13 (2H, s), 2.97 (6H, s), 2.95-2.62 (2H, m), 2.31 (6H, s).

EXAMPLE 15(39)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-t-butylphenylthio)tetrazol-2-yl)pentanoicacid

HPTLC:Rf 0.41 (chloroform:methanol:acetic acid=48:1:1); NMR (DMSO-d₆): δ12.50 (1H, brs), 8.88 (1H, d, J=7.6 Hz), 7.35-7.12 (7H, m), 5.92 (1H, d,J=17.8 Hz), 5.71 (1H, d, J=17.8 Hz), 4.87-4.70 (1H, m), 4.09 (2H, s),2.81 (1H, dd, J=17.3, 5.6 Hz), 2.63 (1H, dd, J=17.3, 7.1 Hz), 2.41 (6H,s), 1.28 (9H, s).

EXAMPLE 15(40)N-(benzylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-t-butylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol:acetic acid=47:2:1); NMR (DMSO-d₆): δ12.57 (1H, brs), 8.98 (1H, d, J=7.0 Hz), 7.40-7.00 (7H, m), 5.69 (2H,s), 4.90-4.72 (1H, m), 4.12 (2H, s), 2.90-2.60 (2H, m), 2.35 (6H, s),1.29 (9H, s).

EXAMPLE 15(41)N-(2-(pyridin-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.23 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.46 (1H, d, J=5.2 Hz), 7.71-7.62 (1H, m), 7.51-7.14 (6H, m), 5.97-5.75(2H, m), 4.51 (2H, s), 4.51-4.34 (3H, m), 3.05 (2H, t, J=6.6 Hz),2.61-2.52 (2H, m).

EXAMPLE 15(42)N-(2-(pyridin-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.14 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.48 (1H, d, J=5.4 Hz), 7.74-7.64 (2H, m), 7.54-7.17 (5H, m), 5.88 (2H,br s), 4.58-4.54 (1H, m), 4.44-4.36 (4H, m), 3.07 (2H, t, J=6.6 Hz),2.71-2.68 (2H, m).

EXAMPLE 15(43)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.27 (chloroform:methanol:acetic acid=50:1:1); NMR(DMSO-d₆): δ13.76-11.14 (1H, br), 8.82 (1H, d, J=6.4 Hz), 7.40-7.07 (5H, m), 6.88(2H, s), 6.02-5.61 (2H, br), 4.90-4.65 (1H, m), 3.20-2.54 (6H, m), 2.99(6H, s).

EXAMPLE 15(44)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.16 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ613.80-11.30 (1H, br), 8.95 (1H, d, J=6.3 Hz), 7.35-7.07 (5H, m), 6.86(2H, s), 5.87-5.45 (2H, br), 4.91-4.72 (1H, m), 3.20-2.53 (6H, m), 2.99(6H, s).

EXAMPLE 15(45)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.46 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.85(1H, d, J=8.8 Hz), 7.72 (1H, d, J=8.8 Hz), 7.63 (1H, d, J=9 Hz), 7.16(2H, d, J=8.4 Hz), 6.83 (2H, d, J=8.4 Hz), 5.88 (2H, s), 4.50 (1H, m),4.16 (2H, m), 3.69 (3H, s), 2.81 (2H, m), 2.62 (2H, m).

EXAMPLE 15(46)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.39 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.86(1H, d, J=8.8 Hz), 7.71 (1H, d, J=8.8 Hz), 7.67 (1H, m), 7.15 (2H, d,J=8.4 Hz), 6.81 (2H, d, J=8.4 Hz), 5.78 (2H, m), 4.52 (1H, m), 4.17 (2H,m), 3.68 (3H, s), 2.82 (2H, m), 2.62 (2H, m).

EXAMPLE 15(47)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.47 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.49(1H, brs), 7.82 (1H, d, J=8.0 Hz), 7.53 (2H, s), 7.17 (2H, d, J=8.4 Hz),6.83 (2H, d, J=8.4 Hz), 5.88 (2H, m), 4.56 (1H, m), 4.18 (2H, t, J=6.6Hz), 3.69 (3H, s), 2.82 (2H, t, J=6.6 Hz), 2.74-2.51 (2H, m), 2.36 (3H,s).

EXAMPLE 15(48)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.43 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.67(1H, d, J=8 Hz), 7.53 (2H, s), 7.15 (2H, d, J=8.6 Hz), 6.81 (2H, d,J=8.6 Hz), 5.74 (2H, m), 4.52 (1H, m), 4.16 (2H, m), 3.68 (3H, m), 2.81(2H, m), 2.63 (2H, m), 2.35 (3H, s).

EXAMPLE 15(49)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.50 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.64(1H, m), 7.14 (2H, d, J=8.2 Hz), 6.85 (2H, s), 6.80 (2H, d, J=8.2 Hz),5.81 (2H, s), 4.49 (1H, m), 4.15 (2H, m), 3.66 (3H, s), 2.97 (6H, s),2.76 (2H, m), 2.60 (2H, m).

EXAMPLE 15(50)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.48 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.65(1H, m), 7.12 (2H, d, J=8.4 Hz), 6.84 (2H, s), 6.79 (2H, d, J=8.4 Hz),5.68 (2H, s), 4.49 (1H, m), 4.15 (2H, m), 3.66 (3H, s), 2.96 (6H, s),2.79 (2H, m), 2.61 (2H, m).

EXAMPLE 15(51)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid hydrochloric acid salt

TLC:Rf 0.33 (chloroform:methanol:acetic acid=48:1:1); NMR (DMSO-d₆): δ7.78 (1H, d, J=8.0 Hz), 7.16 (2H, d, J=8.5 Hz), 6.81 (2H, d, J=8.5 Hz),6.72 (2H, s), 5.79 (2H, s), 4.60-4.40 (1H, m), 4.17 (2H, t, J=6.5 Hz),3.68 (3H, s), 3.00-2.50 (2H, m), 2.96 (6H, s), 2.81 (2H, t, J=6.5 Hz),2.35 (6H, s).

EXAMPLE 15(52)N-(2-(4-methoxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dimethyl-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid hydrochloric acid salt

TLC:Rf 0.25 (chloroform:methanol:acetic acid=48:1:1); NMR (DMSO-d₆): δ7.88 (1H, d, J=8.0 Hz), 7.16 (2H, d, J=8.5 Hz), 6.81 (2H, d, J=8.5 Hz),6.64 (2H, s), 5.57 (2H, s), 4.62-4.43 (1H, m), 4.28-4.10 (2H, m), 3.68(3H, s), 3.00-2.60 (2H, m), 2.96 (6H, s), 2.84 (2H, t, J=7.0 Hz), 2.31(6H, s).

EXAMPLE 15(53)N-(4-(4-methoxyphenyl)butyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.67 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.82(1H, d, J=8.8 Hz), 7.69 (1H, d, J=8.8 Hz), 7.49 (1H, m), 7.06 (2H, d,J=8.6 Hz), 6.78 (2H, d, J=8.6 Hz), 5.93 (2H, m), 4.46 (1H, m), 3.97 (2H,m), 3.68 (3H, s), 2.57 (2H, m), 2.49 (2H, m), 1.53 (4H, m).

EXAMPLE 15(54)N-(4-(4-methoxyphenyl)butyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,3,6-trichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.56 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆):3 7.87(1H, d, J=8.8 Hz), 7.71 (1H, d, J=8.8 Hz), 7.63 (1H, m), 7.06 (2H, d,J=8.6 Hz), 6.80 (2H, d, J=8.6 Hz), 5.80 (2H, m), 4.57 (1H, m), 4.05 (2H,m), 3.70 (3H, s), 2.67 (2H, m), 2.50 (2H, m), 1.57 (4H, m).

EXAMPLE 15(55)N-(4-(4-methoxyphenyl)butyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.61 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.68(1H, d, J=8 Hz), 7.08 (2H, d, J=8.4 Hz), 6.86 (2H, s), 6.80 (2H, d,J=8.4 Hz), 5.86 (2H, s), 4.54 (1H, m), 4.01 (2H, m), 3.70 (3H, s), 2.99(6H, s), 2.80-2.48 (4H, m), 1.57 (4H, m).

EXAMPLE 15(56)N-(4-(4-methoxyphenyl)butyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-dimethylaminophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.53 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.61(1H, d, J=8 Hz), 7.04 (2H, d, J=8.4 Hz), 6.84 (2H, s), 6.78 (2H, d,J=8.4 Hz), 5.71 (2H, s), 4.52 (1H, m), 4.02 (2H, m), 3.69 (3H, s), 2.98(6H, s), 2.63 (2H, m), 2.49 (2H, m), 1.56 (4H, m).

EXAMPLE 15(57)N-(2-(4-methylthiazol-5-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.42 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.40(1H, brs), 8.81 (1H, s), 7.88 (1H, d, J=7.6 Hz), 7.70-7.51 (3H, m), 5.94(2H, s), 4.59 (1H, m), 4.18 (2H, t, J=6.2 Hz), 3.08 (2H, t, J=6.2 Hz),2.79 (1H, dd, J=17 Hz, 5.8 Hz), 2.58 (1H, dd, J=17 Hz, 7.2 Hz), 2.33(3H, s).

EXAMPLE 15(58)N-(2-(4-methylthiazol-5-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.35 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.79(1H, s), 7.83 (1H, d, J=8 Hz), 7.70-7.52 (3H, m), 5.75 (2H, m), 4.60(1H, m), 4.19 (2H, m), 3.10 (2H, t, J=6.4 Hz), 2.71 (2H, m), 2.32 (3H,s).

EXAMPLE 15(59)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.63 (chloroform:methanol:water-40:10:1); NMR (DMSO-d₆): δ 8.69(1H, m), 7.70-7.53 (3H, m), 7.32-7.16 (5H, m), 5.91 (2H, s), 4.73 (1H,m), 3.09 (2H, m), 2.84 (2H, m), 2.55 (2H, m).

EXAMPLE 15(60)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.51 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.85(1H, m), 7.68-7.50 (3H, m), 7.23-7.14 (5H, m), 5.84 (2H, s), 4.76 (1H,m), 3.04 (2H, m), 2.82 (2H, m), 2.65 (2H, m).

EXAMPLE 15(61)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(4-(pyrrolidin-1-ylmethyl)phenylthio)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.39 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ9.02-8.80 (1H, m), 7.66 (2H, d, J=8.5 Hz), 7.50 (2H, d, J=8.5 Hz),7.40-7.10 (5H, m), 5.98 (2H, s), 4.90-4.75 (1H, m), 4.32 (2H, s),3.60-2.93 (6H, m), 2.93-2.55 (4H, m), 2.00-1.80 (4H, m).

EXAMPLE 15(62)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(4-(pyrrolidin-1-ylmethyl)phenylthio)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.36 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ9.04-8.95 (1H, m), 7.65 (2H, d, J=8.2H), 7.57 (2H, d, J=8.2 Hz),7.33-7.10 (5H, m), 5.76 (2H, s), 4.90-4.70 (1H, m), 4.32 (2H, s),3.60-2.95 (6H, m), 2.95-2.54 (4H, m), 2.05-1.90 (4H, m).

EXAMPLE 15(63)N-(2-(4-methylthiazol-5-yl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.38 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.53(1H, brs), 8.95 (1H, d, J=7.4 Hz), 8.79 (1H, s), 7.70-7.50 (3H, m), 5.99(1H, d, J=18.0 Hz), 5.88 (1H, d, J=18.0 Hz), 4.82 (1H, m), 3.04 (4H, s),2.83 (1H, dd, J=17.0 Hz, 5.6 Hz), 2.65 (1H, dd, J=17.0 Hz, 7.0 Hz), 2.32(3H, s).

EXAMPLE 15(64)N-(2-(4-methylthiazol-5-yl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 9.07(1H, d, J=7 Hz), 8.79 (1H, s), 7.69-7.52 (3H, m), 5.87 (1H, d, J=17 Hz),5.74 (1H, d, J=17 Hz), 4.86 (1H, m), 3.06 (4H, s) 2.89 (1H, dd, J=17 Hz,5.8 Hz), 2.75 (1H, dd, J=17 Hz, 7 Hz), 2.28 (3H, s).

EXAMPLE 15(65)N-(butylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.58 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.74(1H, d, J=6.8 Hz), 7.70-7.51 (3H, m), 5.90 (2H, s), 4.75 (1H, m), 2.82(2H, t, J=7.2 Hz), 2.67 (2H, m), 1.51 (2H, m), 1.33 (2H, m), 0.87 (3H,t, J=7.2 Hz).

EXAMPLE 15(66)N-(butylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.43 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.80(1H, d, J=6.6 Hz), 7.69-7.51 (3H, m), 5.82 (2H, m), 4.76 (1H, m), 2.82(2H, m), 2.67 (2H, m), 1.49 (2H, m), 1.31 (2H, m), 0.80 (3H, t, J=7.2Hz).

EXAMPLE 15(67)N-(2-(4-methoxyphenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.52 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.05(1H, brs), 8.82 (1H, m), 7.70-7.66 (3H, m), 7.59-7.54 (1H, m), 7.14 (2H,d, J=8.4 Hz), 6.83 (2H, d, J=8.4 Hz), 5.81 (2H, m), 4.78 (1H, m), 3.70(3H, s), 3.05 (2H, m), 2.86-2.75 (3H, m), 2.62 (1H, dd, J=17 Hz, 8 Hz).

EXAMPLE 15(68)N-(2-(4-methoxyphenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.36(1H, brs), 8.99 (1H, d, J=7.4 Hz), 7.70-7.65 (2H, m), 7.59-7.51 (1H, m),7.11 (2H, d, J=8.6 Hz), 6.79 (2H, d, J=8.6 Hz), 5.89-5.69 (2H, m), 4.84(1H, m), 3.69 (3H, s), 3.09-3.02 (2H, m), 2.94-2.61 (4H, m).

EXAMPLE 15(69)N-(3-(pyrimidin-2-yl)propyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.71 (2H, d, J=5.0 Hz), 7.75-7.48 (3H, m), 7.40 (1H, m), 7.32 (1H, t,J=5.0 Hz), 5.99 (2H, br), 4.48 (1H, m), 4.07 (2H, m), 2.94 (2H, m), 2.59(2H, br), 2.06 (2H, m).

EXAMPLE 15(70)N-(3-(pyrimidin-2-yl)propyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.36 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.66 (2H, m), 7.74-7.46 (4H, m), 7.29 (1H, m), 5.83 (2H, br), 4.50 (1H,m), 4.09 (2H, m), 2.94 (2H, m), 2.63 (2H, m), 2.06 (2H, m).

EXAMPLE 15(71)N-(2-(4-acetylaminophenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.30 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ9.86 (1H, s), 8.77 (1H, d, J=7.4 Hz), 7.75-7.40 (5H, m), 7.13 (2H, d,J=8.2 Hz). 5.90 (2H, brs), 4.83-4.63 (1H, m), 3.04 (2H, t, J=7.3 Hz),2.77 (2H, t, J=7.3 Hz), 2.70-2.50 (2H, m), 2.01 (3H, s).

EXAMPLE 15(72)N-(2-(4-acetylaminophenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ9.85 (1H, s), 8.88-8.76 (1H, m), 7.70-7.50 (3H, m), 7.44 (2H, d, J=8.2Hz), 7.09 (2H, d, J=8.2 Hz), 5.82 (2H, brs), 4.82-4.64 (1H, m),3.13-2.90 (2H, m), 2.90-2.68 (2H, m), 2.68-2.54 (2H, m), 2.01 (3H, s).

EXAMPLE 15(73)N-butyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.55 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ7.70-7.51 (3H, m), 5.93 (2H. s), 4.54 (1H, m), 4.00 (2H, t, J=6.6 Hz),2.77-2.55 (2H, m), 1.55 (2H, m), 1.29 (2H, m), 0.89 (3H, t, J=7.4 Hz).

EXAMPLE 15(74)N-butyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.48 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ7.70-7.52 (3H, m), 5.80 (2H, s), 4.56 (1H, m), 4.01 (2H, m), 2.67 (2H,m), 1.55 (2H, m), 1.30 (2H, m), 0.86 (3H, t, J=7.4 Hz).

EXAMPLE 15(75)N-(propylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.39 (chloroform:methanol:acetic acid=94:3:3); NMR (DMSO-d₆): δ8.61 (1H, d, J=7.0 Hz), 7.70-7.49 (3H, m), 5.95 (2H, brs), 4.75-4.58(1H, m), 2.78 (2H, t, J=7.2 Hz), 2.57 (2H, brs), 1.63-1.40 (2H, m), 0.90(3H, t, J=7.4 Hz).

EXAMPLE 15(76)N-(propylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.30 (chloroform:methanol:acetic acid=94:3:3);

NMR (DMSO-d₆): δ 8.85-8 .68 (1H, m), 7.70-7.50 (3H, m), 5.83 (2H, brs),4.80-4.58 (1H, m), 2.90-2.68 (2H, m), 2.63-2.54 (2H, m), 1.65-1.40 (2H,m), 0.86 (3H, t, J=7.2 Hz).

EXAMPLE 15(77)N-(isopropylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.36 (chloroform:methanol:acetic acid=94:3:3); NMR (DMSO-d₆): δ8.75 (1H, d, J=7.0 Hz), 7.80:7.50 (3H, m), 6.05-5.80 (2H, m), 4.90-4.71(1H, m), 3.49 (1H, sep, J=6.8 Hz), 2.92-2.53 (2H, m), 1.27 (6H, d, J=6.8Hz).

EXAMPLE 15(78)N-(isopropylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.30 (chloroform:methanol:acetic acid=94:3:3); NMR (DMSO-d₆): δ9.03-8.75 (1H, m), 7.80-7.50 (3H, m), 5.76 (2H, brs), 4.90-4.70 (1H, m),3.52 (1H, sep, J=6.6 Hz), 2.95-2.63 (2H, m), 1.28 (6H, d, J=6.6 Hz).

EXAMPLE 15(79)N-(2-methoxyethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.43 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.50(1H, s), 7.93 (1H, d, J=7.8 Hz), 7.71-7.66 (2H, m), 7.59-7.51 (1H, m),5.97 (2H, s), 4.58 (1H, m), 4.13 (2H, m), 3.51 (2H, t, J=4.4 Hz), 3.22(3H, s), 2.80 (1H, dd, J=16.8 Hz, 5.8 Hz), 2.58 (1H, dd, J=16.8 Hz, 4.8Hz).

EXAMPLE 15(80)N-(2-methoxyethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.34 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.00(1H, s), 7.92 (1H, d, J=7 Hz), 7.70-7.66 (2H, m), 7.60-7.53 (1H, m),5.77 (2H, m), 4.60 (1H, m), 4.15 (2H, m), 3.53 (2H, m) 3.25 (3H, s),2.74 (2H, m).

EXAMPLE 15(81)N-(2-cyclohexylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.35 (chloroform:methanol:acetic acid=95:3:2); NMR (DMSO-d₆): δ12.46 (1H, s), 7.78 (1H, d, J=7.6 Hz), 7.73-7.50 (3H, m), 5.96 (2H, s),4.65-4.46 (1H, m), 4.04 (2H, t, J=6.4 Hz), 2.88-2.50 (2H, m), 1.80-0.78(13H, m).

EXAMPLE 15(82)N-(2-cyclohexylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.25 (chloroform:methanol:acetic acid=95:3:2); NMR (DMSO-d₆): δ12.53 (1H, s), 7.92 (1H, d, J=7.6 Hz), 7.77-7.50 (3H, m), 5.80 (2H, s),4.73-4.50 (1H, m), 4.13-3.92 (2H, m), 2.85 (1H, dd, J=17.0, 5.4 Hz),2.29 (1H, dd, J=17.0, 6.6 Hz), 1.80-0.70 (13H, m).

EXAMPLE 15(83)N-cyclohexylmethyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol:acetic acid=95:3:2); NMR (DMSO-d₆): δ12.40 (1H, brs), 7.77 (1H, d, J=7.6 Hz), 7.75-7.50 (3H, m), 5.95 (2H,s), 4.65-4.45 (1H, m), 3.82 (2H, d, J=5.8 Hz), 2.90-2.50 (2H, m),1.80-0.80 (11H, m).

EXAMPLE 15(84)N-cyclohexylmethyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=95:3:2); NMR (DMSO-d₆): δ612.53 (1H, brs), 7.92 (1H, d, J=7.6 Hz), 7.74-7.52 (3H, m), 5.80 (2H,s), 4.70-4.56 (1H, m), 3.96-3.73 (2H, m), 2.85 (1H, dd, J=17.0, 6.2 Hz),2.70 (1H, dd, J=17.0, 6.5 Hz), 1.80-0.80 (11H, m).

EXAMPLE 15(85)N-(2-phenylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ7.69-7.50 (4H, m), 7.32-7.13 (5H, m), 5.85 (2H, s), 4.52 (1H, m), 4.22(2H, m), 2.88 (2H, t, J=7.0 Hz), 2.64 (2H, m).

EXAMPLE 15(86)N-(2-phenylethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.29 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.83(1H, d, J=7.0 Hz), 7.70-7.66 (2H, m), 7.60-7.52 (1H, m), 7.27-7.16 (5H,m), 5.71 (2H, s), 4.59 (1H, m), 4.27 (2H, m), 2.91 (2H, t, J=6.8 Hz),2.70 (2H, m).

EXAMPLE 15(87)N-butyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-acetylaminophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.25 (chloroform:methanol:acetic acid=18:1:1); NMR(DMSO-d₆): δ10.49 (1H, s), 7.87 (2H, s), 7.68 (1H, d, J=7.4 Hz), 5.91 (2H, s),4.62-4.45 (1H, m), 3.99 (2H, t, J=6.4 Hz), 2.80-2.50 (2H, m), 2.10 (3H,s), 1.64-1.20 (4H, m), 0.88 (3H, t, J=7.2 Hz).

EXAMPLE 15(88)N-butyloxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-acetylaminophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.15 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ10.60 (1H, s), 7.87 (2H, s), 7.69 (1H, d, J=8.4 Hz), 5.76 (2H, s),4.60-4.45 (1H, m), 4.07-3.92 (2H, m), 2.73-2.53 (2H, m), 2.10 (3H, s),1.65-1.20 (4H, m), 0.86 (3H, t, J=7.2 Hz).

EXAMPLE 15(89)N-(2-(4-cyanophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.44 (chloroform:methanol:acetic acid=18:1); NMR (DMSO-d₆): δ12.47 (1H, br), 7.84 (1H, d, J=7.0 Hz), 7.79-7.37 and 7.17 (total 7H,m), 5.94 and 5.87 (each 1H, each d, J=16.0 Hz), 4.55 (1H, m), 4.25 (2H,t, J=7.0 Hz), 3.00 (2H, t, J=7.0 Hz), 2.76 and 2.60 (each 1H, each dd,J=16.5, 6.0 Hz).

EXAMPLE 15(90)N-(2-(4-cyanophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.91 (1H, d, J=7.5 Hz), 7.79-7.41 and 7.30-7.08 (total 7H, m) 5.71 (2H,brs), 4.59 (1H, m), 4.28 (2H, t, J=6.5 Hz), 3.01 (2H, t, J=6.5 Hz), 2.73(2H, m).

EXAMPLE 15(91)N-(2-(4-cyanophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.56 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.6-12.3 (1H, br), 7.82 (1H, m), 7.74 (2H, d, J=8.0 Hz), 7.53 (2H, s),7.48 (2H, d, J=8.0 Hz), 5.90 (2H, brs), 4.53 (1H, m), 4.26 (2H, t, J=6.5Hz), 2.99 (2H, t, J=6.5 Hz), 2.65 (2H, m), 2.35 (3H, s).

EXAMPLE 15(92)N-(2-(4-cyanophenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichloro-4-methylphenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.86 (1H, m), 7.72 (2H, d, J=8.0 Hz), 7.52 (2H, s), 7.47 (2H, d, J=8.0Hz), 5.71 (2H, br), 4.58 (1H, m), 4.28 (2H, t, J=6.5 Hz), 3.00 (2H, t,J=6.5 Hz), 2.72 (2H, m), 2.36 (3H, s).

EXAMPLE 15(93)N-(2-methoxyethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.53 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.50(1H, brs), 8.89 (1H, d, J=7.0 Hz), 7.70-7.66 (2H, m), 7.55 (1H, dd,J=9.2 Hz, 6.6 Hz), 6.00 (1H, d, J=18.0 Hz), 5.89 (1H, d, J=18.0 Hz),4.79 (1H, m), 3.45 (2H, t, J=6.6 Hz), 3.24 (3H, s), 2.98 (2H, t, J=6.6Hz), 2.82 (1H, dd, J=17.2 Hz, 5.6 Hz), 2.64 (1H, dd, J=17.2 Hz, 7.0 Hz).

EXAMPLE 15(94)N-(2-methoxyethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.34 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.88(1H, d, J=6.2 Hz), 7.70-7.51 (3H, m), 5.80 (2H, s), 4.79 (1H, m), 3.43(2H, t, J=6.8 Hz), 3.20 (3H, s), 3.00 (2H, t, J=6.8 Hz), 2.70 (2H, d,J=5.8 Hz).

EXAMPLE 15(95)N-(2-(2-methoxyethyloxy)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 7.85(1H, m), 7.71-7.67 (2H, m), 7.60-7.52 (1H, m), 5.94 (2H, s), 4.55 (1H,m), 4.12 (2H, m), 3.58 (2H, m), 3.50 (2H, m), 3.43 (2H, m), 3.22 (3H,s), 2.82-2.55 (2H, m).

EXAMPLE 15(96)N-(2-(2-methoxyethyloxy)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ7.76-7.55 (4H, m), 5.81 (2H, s), 4.55 (1H, m), 4.13 (2H, m), 3.59 (2H,m), 3.56 (2H, m), 3.40 (2H, m), 3.21 (3H, s), 2.66 (2H, m).

EXAMPLE 15(97)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2-chlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.58(1H, m), 8.91 (1H, d, J=7.0 Hz), 7.63-7.59 (1H, m), 7.43-7.17 (8H, m),6.05 (1H, d, J=18.0 Hz), 5.94 (1H, d, J=18.0 Hz), 4.83 (1H, m), 3.10(2H, m), 2.89-2.79 (3H, m), 2.67 (1H, dd, J=17.0 Hz, 7.0 Hz).

EXAMPLE 15(98)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2-chlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 8.81(1H, m), 7.58 (1H, d, J=7.0 Hz), 7.53-7.37 (3H, m), 7.24-7.20 (5H, m),5.80 (2H, s), 4.76 (1H, m), 3.05 (2H, m), 2.81 (2H, m), 2.62 (2H, m).

EXAMPLE 15(99)N-(2-acetylaminoethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.41 (chloroform:methanol:acetic acid=8:1:1); NMR (DMSO-d₆): δ8.67 (1H, d, J=6.4 Hz), 8.06 (1H, d, J=5.8 Hz), 7.74-7.50 (3H, m), 5.98(2H, brs), 4.80-4.55 (1H, m), 3.18 (2H, dt, J=6.4, 5.8 Hz), 2.86 (2H, t,J=5.8 Hz), 2.65-2.50 (2H, m), 1.78 (3H, s).

EXAMPLE 15(100)N-(2-acetylaminoethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=8:1:1); NMR (DMSO-d₆): δ8.90-8.73 (1H, m), 8.10-8.00 (1H, m), 7.75-7.48 (3H, m), 5.84 (2H, brs),4.80-4.60 (1H, m), 3.24-3.10 (2H, m), 3.00-2.75 (2H, m), 2.65-2.50 (2H,m), 1.77 (3H, s).

EXAMPLE 15(101)N-(2-acetylaminoethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 12.40(1H, m), 7.96 (1H, ml, 7.78-7.50 (4H, m), 5.96 (2H, m), 4.57 (1H, m),4.00 (2H, m), 3.26 (2H, m), 2.70 (2H, m), 1.80 (3H, s).

EXAMPLE 15(102)N-(2-acetylaminoethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.45 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 8.00(1H, m), 7.70-7.52 (4H, m), 5.81 (2H, m), 4.57 (1H, m), 4.03 (2H, m),3.29 (2H, m), 2.70 (2H, m), 1.81 (3H, s).

EXAMPLE 15(103)N-(2-(2-methoxyethyloxy)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.41 (chloroform:methanol:water=40:10:1); NMR (CDCl₃): δ7.60-7.20 (4H, m), 6.20-5.40 (2H, m), 5.00-4.60 (1H, m), 3.80-3.40 (6H,m), 3.29 (3H, s), 3.20-3.00 (2H, m), 2.60-2.20 (2H, m).

EXAMPLE 15(104)N-(2-(2-methoxyethyloxy)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.34 (chloroform:methanol:water=40:10:1); NMR (CDCl₃): δ8.00-7.50 (1H, m), 7.50-7.20 (3H, m), 6.20-5.20 (2H, m), 5.00-4.60 (1H,m), 3.80-3.40 (6H, m), 3.32 (3H, s), 3.20-3.00 (2H, m), 2.80 (2H, brs).

EXAMPLE 15(105)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(phenylthio)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.61 (chloroform:methanol:water=40:10:1); NMR(Acetone-_(d6)): δ7.56-7.51 (2H, m), 7.42-7.38 (3H, m), 7.27 (5H, s), 7.18 (1H, m),6.05-5.83 (2H, m), 5.01 (1H, m), 3.18 (2H, m), 2.96-2.89 (4H, m).

EXAMPLE 15(106)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(phenylthio)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.45 (chloroform:methanol:water=40:10:1); NMR(Acetone-_(d6)): δ7.60-7.55 (2H, m), 7.42-7.39 (3H, m), 7.25 (5H, s), 7.17 (1H, m),5.89-5.63 (2H, m), 5.02 (1H, m), 3.20 (2H, m), 2.96-2.88 (4H, m).

EXAMPLE 16(1)-16(4)

By the same procedure as provided in example 1, using the correspondingtetrazole compounds and the corresponding bromo compounds instead ofN-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-bromopentanoicacid.t-butylester, compounds of the present invention having thefollowing physical data were obtained.

EXAMPLE 16(1)N-(2-(4-methoxymethyloxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.60 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.44 (2H, d,J=7.4 Hz), 7.29 (1H, m), 7.14 (2H, d, J=8.4 Hz), 6.96 (2H, d, J=8.4 Hz),5.83 (1H, m), 5.70 (1H, d, J=117.4 Hz), 5.51 (1H, d, J=17.4 Hz), 5.12(2H, s), 4.59 (1H, m), 4.35 (2H, m), 3.45 (3H, s), 3.02-2.87 (3H, m),2.66 (1H, dd, J=17 Hz, 5.0 Hz), 1.42 (9H, s).

EXAMPLE 16(2)N-(2-(4-methoxymethyloxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.52 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.45 (2H, d,J=7.4 Hz), 7.31 (1H, m), 7.16 (2H, d, J=8.6 Hz), 6.98 (2H, d, J=8.6 Hz),5.91 (1H, m), 5.65 (1H, d, J=18.2 Hz), 5.46 (1H, d, J=18.2 Hz), 5.13(2H, s), 4.64 (1H, m), 4.39 (2H, m), 3.46 (3H, s), 3.06 (1H, dd, J=17Hz, 4 Hz), 2.94 (2H, t, J=6.8 Hz), 2.73 (1H, dd, J=17 Hz, 5 Hz), 1.44(9H, s).

EXAMPLE 16(3)N-(2-(4-methoxymethyloxyphenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.55 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.47-7.26 (3H,m), 7.07 (2H, d, J=8.6 Hz), 6.73 (2H, d, J=8.6 Hz), 6.60 (1H, d, J=8.6Hz), 5.66 (1H, d, J=17.8 Hz), 5.47 (1H, d, J=17.8 Hz), 4.82 (1H, m),3.19 (2H, m), 3.02-2.80 (3H, m), 2.66 (1H, dd, J=18 Hz, 4.8 Hz), 1.42(9H, s).

EXAMPLE 16(4)N-(2-(4-methoxymethyloxyphenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.47-7.31 (3H,m), 7.08 (2H, d, J=8.6 Hz), 6.76 (2H, d, J=8.6 Hz), 6.66 (1H, d, J=8.8Hz), 5.99 (1H, d, J=18 Hz), 5.81 (1H, d, J=18Hz), 4.88 (1H, m), 3.23(2H, m), 3.05 (1H, dd, J=17 Hz, 4.4 Hz), 2.89 (2H, m), 2.71 (1H, dd,J=17 Hz, 4.8 Hz), 1.45 (9H, s).

EXAMPLE 17(1)-17(4)

By the same procedure as provided in example 6(1), using the compoundprepared in example 16(1)-16(4), compounds of the present inventionhaving the following physical data were obtained.

EXAMPLE 17(1)N-(2-(4-hydroxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.37 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 9.26(1H, brs), 7.70-7.44 (4H, m), 7.03 (2H, d, J=8.2 Hz), 6.67 (2H, d, J=8.2Hz), 5.94 (2H, m), 4.51 (1H, m), 4.13 (2H, t, J=6.8 Hz), 2.76 (2H, t,J=6.8 Hz), 2.59 (2H, m).

EXAMPLE 17(2)N-(2-(4-hydroxyphenyl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf0.31 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 9.28(1H, brs), 7.70-7.55 (4H, m), 7.02 (2H, d, J=8.4 Hz), 6.60 (2H, d, J=8.4Hz), 5.80 (2H, m), 4.54 (1H, m), 4.17 (2H, m), 2.77 (2H, m), 2.64 (2H,m).

EXAMPLE 17(3)N-(2-(4-hydroxyphenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.30 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 9.27(1H, brs), 8.54 (1H, m), 7.69-7.49 (3H, m), 7.00 (2H, d, J=8.4 Hz), 6.67(2H, d, J=8.4 Hz), 5.96 (2H, m), 4.75 (1H, m), 3.00 (2H, m), 2.71 (2H,m), 2.59 (2H, m).

EXAMPLE 17(4)N-(2-(4-hydroxyphenyl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 9.24(1H, brs), 8.73 (1H, d, J=7 Hz), 7.68-7.51 (3H, m), 6.95 (2H, d, J=8.2Hz), 6.62 (2H, d, J=8.2 Hz), 5.85 (2H, m), 4.77 (1H, m), 2.98 (2H, m),2.70-2.61 (4H, m).

REFERENCE EXAMPLE 9(1)3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester.hydrochloric acid salt

The mixture of the compound prepared in example 5(1) (8.74 9), ethanol(600 ml), 10% palladium on activated carbon (773 mg) and a 6N aqueoussolution of hydrochloric acid (5.37 ml) was stirred for 20 min at roomtemperature under an atmosphere of hydrogen gas. The reaction mixturewas filtered through Celite (trade mark) and the filtrate wasconcentrated to give the title compound having the following physicaldata.

TLC:Rf 0.36 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 9.10-8.40 (3H,br), 7.55 (1H, d, J=9.0 Hz), 7.55 (1H, d, J=7.2 Hz), 7.40 (1H, dd, J=9.0Hz, 7.2 Hz), 6.11 (2H, br), 4.75-4.55 (1H, m), 4.41 (2H, s), 3.50-3.05(2H, m), 1.44 (9H, s).

REFERENCE EXAMPLE 9(2) AND REFERENCE EXAMPLE 9(3)

By the same procedure as provided in reference example 9(1), using thecompound prepared in example 5(2) or example 5(3), the title compoundshaving the following physical data were obtained.

REFERENCE EXAMPLE 9(2)3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester.hydrochloric acid salt

TLC:Rf 0.32 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 8.60-8.35 (3H,br), 7.52 (2H, each d, J=9.0, 6.8 Hz), 7.37 (1H, dd, J=9.0, 6.8 Hz),6.14 and 6.03 (each 1H, d, J=17.5 Hz), 4.60-4.46 (1H, m), 4.54 (2H, s),3.28-2.99 (2H, m), 1.41 (9H, s).

REFERENCE EXAMPLE 9(3)3-amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester.hydrochloric acid salt

TLC:Rf 0.54 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 8.66 (2H, brs),7.31 (5H, s), 5.96 (2H, s), 4.63 (1H, brs), 4.20 (2H, s), 3.17 (2H, m),1.44 (9H, s).

EXAMPLE 18(1)3-(N-(2-(hexahydro-2-oxo-3S-(thiazol-4-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

To a solution of 2-(hexahydro-2-oxo-3S-(thiazol-4-ylcarbonylamino)azepin-1-yl)propionic acid (414 mg) in dichloromethane (4 ml) anddimethylformamide (1 ml) was added 1-hydroxybenzotriazole (306 mg) and1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (383 mg) at 0° C. Themixture was stirred for 15 min at room temperature. To the mixture wasadded the compound prepared in reference example 9 (1) (600 mg) indimethylformamide (3 ml) and triethylamine (0.204 ml) at 0° C. Thereaction mixture was stirred for 1 h at room temperature. The reactionmixture was quenched by addition of water, and extracted with ethylacetate. The extract was washed with a saturated aqueous solution ofsodium chloride, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (chloroform:methanol=100:1→29:1) to give the compound of thepresent invention (682 mg) having the following physical data.

TLC:Rf 0.55 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 9.17 (1H, m),8.94-8.51 (2H, m), 8.30 (1H, m), 7.52-7.25 (3H, m), 5.82 (2H, m),5.27-4.68 (3H, m), 4.34 (2H, m), 3.65-3.42 (2H, m), 2.91-2.56 (2H, m),2.08-1.52 (6H, m), 1.39 (9H, s), 1.33 (3H, m).

EXAMPLE 18(2)-18(28)

By the same procedure as provided in example 18(1), using thecorresponding carboxylic acid compounds and the compound prepared inreference example 9(1), reference example 9(2) or reference example9(3), the compounds of the present invention having the followingphysical data were obtained.

EXAMPLE 18(2)3-(N-(2-(hexahydro-2-oxo-3S-(thiazol-4-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.65 (chloroform:methanol=9:1); NMR (CDCl₃): δ 9.19-9.08 (1H, m),8.85-8.50 (2H, m), 8.35-8.29 (1H, m), 7.27 (5H, m), 5.67 (2H, m),5.26-4.69 (3H, m), 4.13 (2H, m), 3.58-3.20 (2H, m), 2.86-2.56 (2H, m),2.07-1.43 (6H, m), 1.38-1.29 (12H, m).

EXAMPLE 18(3)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.34 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 8.92 (1H, m),8.64 (1H, m), 8.51 (2H, m), 8.08 (1H, m), 7.42 (1H, m), 7.21 (5H, s),5.59 (2H, s), 5.13-4.57 (3H, m), 4.05 (2H, m) 3.40 (2H, m), 2.71-2.50(2H, m), 1.82 (6H, m), 1.33 (9H, s), 1.28 (3H, m).

EXAMPLE 18(4)3-(N-(2-(hexahydro-2-oxo-3S-(quinolin-2-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.69 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 9.30 (1H, m),8.86-8.54 (2H, m), 8.19-8.05 (2H, m), 7.99-7.68 (3H, m), 7.24 (5H, m),5.70 (2H, m), 5.28-4.66 (2H, m), 4.14 (2H, m), 3.62-3.23 (2H, m),2.82-2.38 (2H, m), 2.21-1.48 (6H, m), 1.37 (12H, m).

EXAMPLE 18(5)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-2-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.61 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 9.11 (1H, m),8.86-8.51 (2H, m), 8.04 (2H, m), 7.62 (1H, m), 7.27 (5H, m), 5.67 (2H,m), 5.24-4.65 (2H, m), 4.11 (2H, m), 3.52 (1H, m), 3.24 (1H, m), 2.80(1H, m), 2.56 (1H, m), 2.06-1.45 (6H, m), 1.38 (9H, s), 1.34 (3H, s).

EXAMPLE 18(6) and 18(7)3-(N-(2-(hexahydro-2-oxo-3S-(morpholin-1-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

(wherein * represents mixture of R and S stereochemistry. The compoundswere separated to the compound of example 19(6) and example 19(7) byhydrolysis of t-butylester)

NMR (DMSO-d₆): δ 8.63-8.39 (1H, m), 7.25 (5H, m), 6.35 (1H, t-like),5.58 (2H, m), 5.11-4.28 (2H, m), 4.08 (2H, s), 3.45 (6H, m), 3.15 (2H,m), 2.76 (1H, m), 2.50 (1H, m), 1.75-1.40 (6H, m), 1.34 (9H, s), 1.26(3H, m).

EXAMPLE 18(8)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-4-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.57 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 8.66 (4H, m),7.72 (2H, m), 7.27 (5H, m), 5.65 (2H, ), 5.18-4.63 (2H, m), 3.60-3.34(2H, m), 2.80 (1H, m), 2.54 (2H, m), 1.93-1.58 (6H, m), 1.39 (9H, m),1.33 (3H, m).

EXAMPLE 18(9) 3-(N-(2-(hexahydro-2-oxo-3S-(4-methoxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

NMR (DMSO-d₆): δ 8.55 (1H, d, J=6.5 Hz), 8.02 (1H, d, J=6.5 Hz), 7.80(2H, dd, J=8.0, 2.0 Hz), 7.40-7.18 (5H, m), 6.98 (2H, d, J=8.0 Hz), 5.66(2H, s), 5.10 (1H, q, J=6.0 Hz), 4.90-4.60 (2H, m), 4.20-4.10 (2H, m),3.80 (3H, s), 2.88-2.50 (4H, m), 2.35-1.20 (9H, m), 1.14 (9H, S).

EXAMPLE 18(10)3-(N-(2-(hexahydro-2-oxo-3S-(3-methoxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

NMR (DMSO-d₆): δ 8.58 (1H, d, J=7.0 Hz), 8.20 (1H, d, J=7.0 Hz),7.40-7.20 (8H, m), 7.15-7.00 (1H, m), 5.65(2H, s), 5.34-5.05 (1H, q,J=6.5 Hz), 4.92-4.65 (2H, m), 4.12 (2H, s), 3.80 (3H, s), 2.95-2.50 (4H,m), 2.05-1.20 (9H, m), 1.15 (9H, s).

EXAMPLE 18(11) 3-(N-(2-(hexahydro-2-oxo-3S-(4-(morpholin-1-ylcarbonyl)phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

NMR (DMSO-d₆): δ 8.60-8.58 (2H, m), 7.92 (2H, t, J=8.0 Hz), 7.52-7.40(2H, m), 7.32-7.15 (5H, m), 5.82-5.58 (2H, m), 5.20-5.10 (1H, m),5.00-4.8 (1H, m), 4.70-4.50 (1H, m), 4.15 (2H, brs), 3.80-3.20 (8H, m),2.78-2.42 (4H, m), 2.00-1.50 (7H, m), 1.45-1.20 (3H, m), 1.20 (9H, s).

EXAMPLE 18(12) and (13)3-(N-(2-(hexahydro-2-oxo-3S-(quinolin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

(wherein * represents mixture of R and S stereochemistry. The compoundswere separated to the compound of example 19(12) and example 19(13) byhydrolysis of t-butylester)

TLC:Rf 0.71 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 9.37-9.24 (2H,m), 8.88-8.51 (2H, m), 8.23 (2H, m), 7.96-7.81 (2H, m), 7.26 (5H, m),5.68 (2H, m), 5.30-4.67 (2H, m), 4.14 (2H, m), 3.56 (1H, m), 3.29 (1H,m), 2.81 (1H, m), 2.58 (1H, m), 2.13-1.49 (6H, m), 1.38 (12H, s).

EXAMPLE 18(14)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.46 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 8.99 (1H, m),8.81-8.53 (3H, m), 8.14 (1H, m), 7.48 (4H, m), 5.79 (2H, m), 5.22-4.69(3H, m), 4.35 (2H, m), 3.63-3.40 (2H, m), 2.86 (1H, m), 2.56 (1H, m),1.95-1.48 (6H, m), 1.39 (9H, m), 1.33 (3H, m).

EXAMPLE 18(15)3-(N-(2-(hexahydro-2-oxo-3S-(4-dimethylaminophenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

NMR (CDCl₃): δ 8.75 (1H, m), 7.90-7.50 (4H, m), 7.40-7.10 (8H, m), 6.70(2H, d, J=10 Hz), 6.54 (1H, d, J=8.5 Hz), 5.60 (2H, m), 5.25-5.10 (1H,m), 4.90-4.60 (5H, m), 3.20-2.50 (3H, m), 2.65 (6H, s), 2.15-1.60 (8H,m), 1.45 (3H, d, J=7.5 Hz), 1.15 (9H, s).

EXAMPLE 18(16)

3-(N-(2S-(2-phenyl-4R-methyl-4,5-dihydrothiazol-4-ylcarbonylamino)propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.58 and 0.60 (hexane:ethyl acetate=1:3); NMR (CDCl₃): δ7.90-7.75 (1H, m), 7.60-7.10 (7H, m), 6.90-5.35 (2H, m), 4.90-4.70 (1H,m), 4.60-4.30 (2H, m), 3.90-3.70 (2H, m), 3.40-3.30 (1H, m), 3.10-2.90(1H, m), 2.80-2.50 (1H, m), 1.60 (9H, s), 1.60-1.35 (6H, m).

EXAMPLE 18(17)3-(N-(2S-(2-phenyl-4,5-dihydrothiazol-4-ylcarbonylamino)propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.62 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.90-7.70 (1H, m),7.60-6.90 (7H, m), 5.90-5.75 (1H, m), 5.65-5.40 (1H, m), 5.30-5.10 (1H,m), 4.95-4.70 (1H, m), 4.65-4.10 (2H, m), 4.00-3.55 (2H, m), 3.40-3.15(1H, m), 3.15-2.95 (1H, m), 2.85-2.65 (1H, m), 1.60-1.05 (12H, m).

EXAMPLE 18(18)N-(thiazol-4-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.37 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.81 (1H, d,J=2.0 Hz), 8.26 (1H, d, J=2.0 Hz), 7.33 (1H, d, J=8.6 Hz), 7.33 (1H, d,J=7.4 Hz), 7.16 (1H, dd, J=8.6 Hz, 7.4 Hz), 5.85 and 5.63 (each 1H, d,J=18.0 Hz), 5.17-5.02 (1H, m), 4.59 (2H, s), 3.19 (1H, dd, J=117.5 Hz,4.6 Hz), 2.76 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.45 (9H, s).

EXAMPLE 18(19)N-phenylthiomethylcarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.58 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.94 (1H, d,J=9.0 Hz), 7.39-7.22 (8H, m), 5.16 (2H, s), 4.81 (1H, dt, J=9.0, 4.6Hz), 4.58 (2H, s), 3.83 (1h, d, J=17.0 Hz), 3.68 (1h, d, J=17.0 Hz),2.95 (1H, dd, J=17.5, 4.7 Hz), 2.46 (1H, dd, J=17.5, 4.7 Hz), 1.40 (9H,s).

EXAMPLE 18(20)N-(perhydrobenzo-1,4-diazepin-2,5-dion-3-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.30 (chloroform:methanol=8:1); NMR (CDCl₃): δ 69.50-8.90 (1H,m), 8.50-8.10 (1H, m), 7.90-7.80 (1H, m), 7.60-7.10 (6H, m), 7.10-6.80(1H, m), 5.80-5.30 (1H, m), 4.90-4.60 (1H, m), 4.50-4.00 (2H, m),3.20-2.50 (2H, m), 1.50-1.20 (9H, m).

EXAMPLE 18(21)3-(N-(2-(hexahydro-2-oxo-3S-(3-t-butoxycarbonylphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 8.78-8.48 (2H,m), 8.34 (1H, m), 8.06 (2H, m), 7.58 (1H, m), 7.25 (5H, m), 5.65 (2H,s), 5.23-4.65 (3H, m), 4.12 (2H, m), 3.61-3.35 (2H, m), 2.80 (1H, m),2.54 (1H, m), 94-1.61 (6H, m), 1.57 (9H, s), 1.38 (9H, s), 1.34 (3H, m).

EXAMPLE 18(22)3-(N-(2-(hexahydro-2-oxo-3S-(4-t-butoxycarbonylphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.58 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 8.81-8.45 (2H,m), 7.93 (4H, m), 7.26 (5H, m), 5.66 (2H, m), 5.23-4.64 (3H, m), 4.13(2H, m), 3.61-3.28 (2H, m), 2.81 (1H, m), 2.55 (1H, m), 1.97-1.47 (6H,m), 1.57 (9H, s), 1.38 (9H, s), 1.34 (3H, m).

EXAMPLE 18(23)N-(1-benzyloxycarbonylpiperidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 18(24))

TLC:Rf 0.52 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 8.80-8.65 (1H,m), 7.60-7.15 (8H, m), 5.90-5.67 (2H, m), 5.06 (2H, brs), 4.99-4.81 and4.81-4.65 (each 1H, m), 4.51-4.15 (2H, m), 4.02-3.80 (1H, m), 3.45-2.95(1H, m), 2.95-2.55 (2H, m), 2.20-2.00 (2H, 1.80-1.10 (5H, m), 1.39 (9H,s).

EXAMPLE 18(24)N-(1-benzyloxycarbonylpiperidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 18(23))

TLC:Rf 0.44 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 9.00-8.75 (1H,m), 7.57-7.15 (8H, m), 5.98-5.50 (2H, m), 5.14-4.90 (2H, m), 4.90-4.65(2H, m), 4.44-4.14 (2H, m), 4.05-3.98 (1H, m), 3.45-2.95 (1H, m),2.95-2.45 (2H, m), 2.21-2.05 (1H, m), 1.80-1.10 (5H, m), 1.40 (9H, s).

EXAMPLE 18(25)N-(1-acetylpiperidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.40 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 8.87-8.51 (1H,m), 7.58-7.20 (3H, m), 5.93-5.60 (2H, m), 5.11-4.47 (2H, m), 4.47-4.07and 3.80-3.60 (3H, m), 3.40-3.13 (1H, m), 2.98-2.56 (2H, m), 2.22-1.90(1H, m), 2:04 and 1.99 (total 3H, each s), 1.75-1.10 (5H, m), 1.40 (9H,s).

EXAMPLE 18(26)N-(1-benzyloxycarbonylpyrrolidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 18(27))

TLC:Rf 0.30 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.76-7.55 (1H,br), 7.42-7.14 (8H, m), 5.90-5.33 (2H, m), 5.12 (2H, s), 4.96-4.62 (1H,m), 4.31 (3H, brs), 3.81-3.34 (2H, m), 3.17-2.50 (2H, m), 2.45-1.78 (4H,m), 1.44 (9H, s).

EXAMPLE 18(27)N-(1-benzyloxycarbonylpyrrolidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 18(26))

TLC:Rf 0.24 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.86-7.64 (1H,m), 7.45-7.10 (8H, m), 5.95-5.35 (2H, m), 5.31-5.00 (2H, m), 4.95-4.60(1H, m), 4.52-4.34 (1H, m), 4.27 (2H, s), 3.77-3.33 (2H, br), 3.15-2.50(2H, m), 2.44-1.73 (4H, m), 1.43 (9H, s).

EXAMPLE 18(28)N-(1-acetylpyrrolidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.19 (ethyl acetate); NMR (CDCl₃): δ 9.05 and 8.86 (total 1H,each d, J=7.0 and 7.4 Hz), 7.64-7.30 (3H, m), 6.01-5.64 (2H, m),4.99-4.54 (1H, m), 4.54-3.98 (1H, m), 4.34 and 4.26 (total 2H, each s),3.80-3.23 (2H, m), 3.00-2.38 (2H, m), 2.34-1.57 (4H, m), 1.99 and 1.95(total 3H, each s), 1.41 (9H, s).

EXAMPLE 19 (1)-19 (26)

By the same procedure as provided in example 6(1), using the compoundprepared in example 18(1)-18(20) or example 18(23)-18(28), the compoundsof the present invention having the following physical data wereobtained.

EXAMPLE 19 (1)3-(N-(2-(hexahydro-2-oxo-3S-(thiazol-4-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.57 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ9.18-9.08 (1H, m), 8.75-8.50 (2H, m), 8.34-8.29 (1H, m), 7.52-7.26 (3H,m), 6.02-5.69 (2H, m), 5.24-4.63 (3H, m), 4.35 (2H, m), 3.62-3.30 (2H,m), 2.70 (2H, m), 2.07-1.44 (6H, m), 1.39-1.27 (3H, m).

EXAMPLE 19 (2)3-(N-(2-(hexahydro-2-oxo-3S-(thiazol-4-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoic acid

TLC:Rf 0.57 (chloroform:methanol:water=6:4:1); NMR (CDCl₃): δ 12.72 (1H,brs), 9.13 (1H, m), 8.90-8.49 (2H, m), 8.30 (1H, m), 7.27 (5H, m), 5.69(2H, m), 5.23-4.65 (3H, m), 4.14 (2H, m), 3.48 (2H, m), 2.90-2.54 (2H,m), 2.05-1.41 (6H, m), 1.32 (3H, m).

EXAMPLE 19 (3)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.54 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 12.60(1H, brs), 8.98 (1H, m), 8.69-8.58 (3H, m), 8.13 (1H, m), 7.47 (1H, m),7.27 (5H, m), 5.66 (2H, m), 5.20-4.61 (3H, m), 4.11 (2H, m), 3.42 (2H,m), 2.72 (2H, m), 1.87 (6H, m), 1.32 (3H, m).

EXAMPLE 19 (4)3-(N-(2-(hexahydro-2-oxo-3S-(quinolin-2-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.51(1H, m), 9.34 (1H, dd, J=6.4 Hz, 0.8 Hz), 8.66 (1H, m), 8.60 (1H, d,J=8.4 Hz), 8.19 (1H, d, J=8.4 Hz), 8.08 (2H, m), 7.88 (1H, m), 7.77 (1H,m), 7.22 (5H, m), 5.70 (2H, s), 5.24 (1H, m), 4.80 (2H, m), 4.13 (2H,m), 3.62-3.22 (2H, m), 2.84 (1H, m), 2.56 (1H, m), 2.14-1.23 (6H, m),1.37 (3H, d, J=7.0 Hz).

EXAMPLE 19 (5)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-2-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.70 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 9.12(1H, m), 8.64 (2H, m), 8.02 (2H, m), 7.62 (1H, m), 7.27 (5H, m), 5.67(2H, m), 5.26-4.74 (3H, m), 4.14 (2H, m), 3.40 (2H, m) 2.90-2.59 (2H,m), 2.08-1.43 (6H, m), 1.32 (3H, m).

EXAMPLE 19 (6)3-(N-(2-(hexahydro-2-oxo-3S-(morpholin-1-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 18(7))

TLC:Rf 0.62 (chloroform:methanol:water=6:4:1);

NMR (DMSO-d₆): δ 12.53 (1H, brs), 8.52 (1H, m), 7.27 (5H, m), 6.43 (1H,m), 5.66 (2H, s), 5.12 (1H, m), 4.74 (1H, m), 4.52 (1H, m), 4.13 (2H,m), 3.52 (4H, m), 3.44 (2H, m), 3.24 (4H, m), 2.81 (1H, m), 2.60 (1H,m), 1.85-1.37 (6H, m), 1.30 (3H, m).

EXAMPLE 19 (7)3-(N-(2-(hexahydro-2-oxo-3S-(morpholin-1-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 18(6))

TLC:Rf 0.59 (chloroform:methanol:water=6:41); NMR (DMSO-d ): δ 12.56(1H, brs), 8.68-8.48 (1H, m), 7.30 (3H, m), 6.42 (1H, m), 5.66 (2H, m),4.66 (2H, m), 4.41 (1H, m), 4.13 (2H, m), 3.48 (4H, m), 3.42 (2H, m),3.17 (4H, m), 2.82 (1H, m), 2.61 (1H, m), 1.80-1.42 (6H, m), 1.30 (3H,m)

EXAMPLE 19 (8)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-4-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.59 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 8.70(4H, m), 7.73 (2H, m), 7.26 (5H, m), 5.67 (2H, m), 5.19-4.65 (3H, m),4.13 (2H, m), 3.55 (2H, m), 2.83 (1H, m), 2.60 (1H, m) 1.94-1.60 (6H,m), 1.32 (3H, m).

EXAMPLE 19 (9)3-(N-(2-(hexahydro-2-oxo-3S-(4-methoxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.50 (chloroform:methanol:water=50:10:1); NMR (DMSO-d₆):6 8.58(1H, d, J=6.5 Hz), 8.05 (1H, d, J=6.5 Hz), 7.80 (2H, dd, J=8.0, 2.0 Hz),7.40-7.18 (5H, m), 6.98 (2H, d, J=8.0 Hz), 5.62 (2H, s), 5.08 (1H, q,J=6.0 Hz), 4.90-4.60 (2H, m), 4.20-4.00 (2H, m) 3.80 (3H, s), 2.88-2.50(4H, m), 2.05-1.20 (9H, m).

EXAMPLE 19 (10)3-(N-(2-(hexahydro-2-oxo-3S-(3-methoxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.48 (chloroform:methanol:water=50:10:1); NMR (DMSO-d₆): δ 8.58(1H, d, J=7.0 Hz), 8.20 (1H, d, J=7.0 Hz), 7.40-7.20 (8H, m), 7.15-7.00(1H, m), 5.65(2H, s), 5.30-5.10 (1H, q, J=6.5 Hz), 4.92-4.65 (2H, m),4.12 (2H, s), 3.80 (3H, s), 2.95-2.50 (4H, m), 2.05-1.20 (9H, m).

EXAMPLE 19 (11) 3-(N-(2-(hexahydro-2-oxo-3S-(4-(morpholin-1-ylcarbonyl)phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.45 (chloroform:methanol:water=70:30:1); NMR (DMSO-d₆): δ8.60-8.58 (2H, m), 7.92 (2H, t, J=8.0 Hz), 7.52-7.40 (2H, m), 7.32-7.15(5H, m), 5.82-5.58 (2H, m), 5.20-5.10 (1H, m), 5.00-4.8 (1H, m),4.70-4.50 (1H, m), 4.15 (2H, brs), 3.80-3.20 (8H, m), 2.78-2.42 (4H, m),2.00-1.50 (7H, m), 1.45-1.20 (3H, m).

EXAMPLE 19 (12)3-(N-(2-(hexahydro-2-oxo-3S-(quinolin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet.)

TLC:Rf 0.30 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆): δ 12.40(1H, brs), 9.38 (1H, s), 9.35 (1H, m), 8.81 (1H, m), 8.57 (1H, s), 8.27(2H, m), 7.89 (2H, m), 7.26 (5H, m), 5.68 (2H, m), 5.24 (1H, m), 4.82(2H, m), 4.14 (2H, m), 3.55-3.27 (2H, m), 2.84 (1H, m), 5.58 (1H, m),2.15-1.46 (6H, m), 1.37 (3H, m).

EXAMPLE 19 (13)3-(N-(2-(hexahydro-2-oxo-3S-(quinolin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.30 and 0.25 (chloroform:methanol:water=40:10:1); NMR (DMSO-d₆):δ 12.50 (1H, brs), 9.25 (2H, m), 8.86-8.67 (1H, m), 8.54 (1H, s), 8.21(2H, m), 7.85 (2H, m), 7.27 (5H, m), 5.72 (2H, m), 4.81 (3H, m), 4.12(2H, m), 3.52 (2H, m), 2.87 (1H, m), 2.67 (1H, m), 2.07-1.52 (6H, m),1.34 (3H, m).

EXAMPLE 19 (14)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.55 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 12.50(1H, brs), 8.99 (1H, m), 8.81-8.52 (3H, m), 8.19-8.08 (1H, m), 7.55-7.26(4H, m), 5.98-5.67 (2H, m), 5.24-4.70 (3H, m), 4.32 (2H, m), 3.80-3.37(2H, m), 2.96-2.61 (2H, m), 1.95-1.57 (6H, m), 1.35 (3H, m).

EXAMPLE 19 (15)3-(N-(2-(hexahydro-2-oxo-3S-(4-dimethylaminophenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:water=70:30:1); NMR (CDCl₃): δ 8.75(1H, m), 7.90-7.50 (4H, m), 7.40-7.10 (8H, m), 6.65 (2H, d, J=l O Hz),6.54 (1H, d, J=8.5 Hz), 5.60 (2H, m), 5.25-5.10 (1H, m), 4.90-4.60 (5H,m), 3.20-2.50 (3H, m), 2*65 (6H, s), 2.15-1.60 (8H, m), 1.35 (3H, d,J=7.5 Hz).

EXAMPLE 19 (16)3-(N-(2S-(2-phenyl-4R-methyl-4,5-dihydrothiazol-4-ylcarbonylamino)propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.18 (chloroform:methanol:water=100:20:1); NMR (DMSO-d₆): δ 8.93(d, J=8 Hz) and 8.80 (d, J=8 Hz) total 1H, 7.90-7.70 (3H, m), 7.60-7.20(6H, m), 5.90-5.60 (2H, m), 4.80-4.60 (1H, m), 4.50-4.10 (3H, m),2.90-2.70 (2H, brd), 1.45 (3H, s), 1.30 (3H, d, J=8 Hz).

EXAMPLE 19 (17)3-(N-(2S-(2-phenyl-4,5-dihydrothiazol-4-ylcarbonylamino)propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.48 (chloroform:methanol:acetic acid=10:1:1); NMR (DMSO-d₆): δ8.90-8.70 (1H, m), 8.50-8.20 (1H, m), 7.85-7.75 (2H, m), 7.60-7.20 (6H,m), 6.10-5.50 (2H, m), 5.30-5.15 (1H, m), 4.60-4.15 (4H, m), 3.80-3.10(2H, m), 2.80-2.40 (2H, m), 1.40-1.20 (3H, m).

EXAMPLE 19 (18)N-(thiazol-4-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.47 (chloroform:methanol:acetic acid=18:1:1); NMR(DMSO-d₆): δ12.70-12.20 (1H, br), 9.10-8.90 (1H, m), 8.45 and 8.44 (1H, each s),8.31 (1H, s), 7.56-7.45 and 7.45-7.27 (total 3H, m), 6.04-5.75 (2H, m),5.13-4.96 (1H, m), 4.50 (2H, s). 3.05-2.67 (2H, m).

EXAMPLE 19 (19)N-phenylthiomethylcarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.54 (chloroform:methanol:acetic acid=25:1:1); NMR (DMSO-d₆): δ12.72-12.20 (1H, br), 8.83 (1H, d), 7.54-7.18 (8H, m), 5.69 (2H, s),4.79-4.70 (1H, m), 4.51 (2H, s), 3.77 (2H, s), 2.80-2.72 (2H, m).

EXAMPLE 19 (20)N-(perhydrobenzo-1,4-diazepin-2,5-dion-3-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.25 (chloroform:methanol:acetic acid=10:1:1); NMR (DMSO-d₆): δ10.7-10.5 (1H, m), 9.10-8.70 (1H, m), 8.10-7.85 (1H, m), 7.80-7.70 (1H,m), 7.60-7.10 (6H, m), 6.10-5.70 (2H, m), 4.85-4.75 (1H, m), 4.60-4.40(1H, m), 4.40-4.10 (2H, m), 2.90-2.60 (2H, m).

EXAMPLE 19 (21)N-(1-benzyloxycarbonylpiperidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The above compound has theopposite stereoconfiguration as the compound of example 19(22))

TLC:Rf 0.39 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.40-11.80 (1H, br), 8.94-8.65 (1H, m), 7.58-7.13 (8H, m), 5.92-5.62(2H, m), 5.06 (2H, brs), 4.90-4.65 (2H, m), 4.42-4.19 (2H, m), 4.01-3.77(1H, m), 3.47-2.99 (1H, m), 2.99-2.60 (2H, m), 2.21-2.00 (1H, m),1.75-1.47 and 1.47-1.15 (5H, m).

EXAMPLE 19 (22)N-(1-benzyloxycarbonylpiperidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The above compound has theopposite stereoconfiguration as the compound of example 19(21))

TLC:Rf 0.39 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.60-11.90 (1H, br), 8.93-8.65 (1H, m), 7.58-7.07 (8H, m), 5.92-5.60(2H, m), 5.06 (2H, brs), 4.90-4.65 (2H, m), 4.42-4.19 (2H, m), 4.01-3.77(1H, m), 3.47-2.99 (1H, m), 2.99-2.60 (2H, m), 2.21-2.00 (1H, m),1.75-1.47 and 1.47-1.15 (5H, m).

EXAMPLE 19 (23)N-(1-acetylpiperidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.58 (chloroform:methanol:acetic acid=8:1:1); NMR (DMSO-d₆): δ8.82-8.52 (1H, m), 7.60-7.20 (3H, m), 5.95-5.60 (2H, m), 5.10-4.95,4.95-4.55 and 4.40-4.10 (5H, m), 3.75-3.60 (1H, m), 3.00-2.53 (2H, m),2.33-1.95 (1H, m), 2.03 and 2.00 (total 3H, each s), 1.75-1.10 (5H, m).

EXAMPLE 19 (24)N-(1-benzyloxycarbonylpyrrolidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 19(25))

TLC:Rf 0.40 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ9.16-8.73 (1H, m), 7.72-7.01 (8H, m), 6.00-5.40 (2H, m), 5.22-4.84 (2H,m), 4.84-4.80 (1H, m), 4.80-4.04 (3H, m), 3.70-3.23 (2H, m), 2.98-2.40(2H, m), 2.40-1.57 (4H, m).

EXAMPLE 19 (25)N-(1-benzyloxycarbonylpyrrolidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

(wherein * represents R or S stereochemistry. The stereostructure hasnot been identified yet. However, the above compound has the oppositestereoconfiguration as the compound of example 19(24))

TLC:Rf 0.40 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-dd): δ9.22-8.66 (1H, m), 7.75-7.10 (8H, m), 6.06-5.40 (2H, m), 5.21-4.84 (2H,m), 4.84-4.56 (1H, m), 4.56-4.00 (3H, m), 3.70-3.23 (2H, m), 3.00-2.40(2H, m), 2.40-1.40 (4H, m).

EXAMPLE 19 (26)N-(1-acetylpyrrolidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.13 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ9.07-8.54 (1H, m), 7.67-7.23 (3H, m), 6.18-5.59 (2H, m), 4.92-4.02 (4H,m), 3.71-3.20 (2H, m), 2.92-2.39 (2H, m), 2.39-1.50 (4H, m), 1.96 and1.89 (total 3H, each s).

EXAMPLE 20(1)-20(2)

By the same procedure as provided in example 6(1), using the compoundprepared in example 18(21) or 18(22), the compounds of the presentinvention having the following physical data were obtained.

EXAMPLE 20(1) 3-(N-(2-(hexahydro-2-oxo-3S-(3-carboxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.38 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 12.84(2H, brs), 8.54 (2H, m), 8.41 (1H, s) 8.07 (2H, m), 7.59 (1H, m), 7.26(5H, m), 5.66 (2H, m), 5.24-4.62 (3H, m), 4.13 (2H, m), 3.39 (2H, m),2.83 (1H, m), 2.60 (1H, m) 1.97-1.55 (6H, m), 1.33 (3H, m).

EXAMPLE 20(2) 3-(N-(2-(hexahydro-2-oxo-3S-(4-carboxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

TLC:Rf 0.39 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 8.57(1H, m), 8.44 (1H, m), 8.04-7.89 (4H, m), 7.27 (5H, m), 5.66 (2H, m),5.22-4.67 (3H, m), 4.13 (2H, m), 3.53 (2H, m), 2.83 (1H, m), 2.65 (1H,m), 1.99-1.53 (6H, m), 1.34 (3H, m).

REFERENCE EXAMPLE 103-(N-(2-(hexahydro-2-oxo-3S-(1-((2-trimethylsilyl)ethoxymethyl)imizazol-5-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.t-butylester

By the same procedure as provided in example 18(1), using the compoundprepared in reference example 9(3) and2-(hexahydro-2-oxo-3S-(1-((2-trimethylsilyl)ethoxymethyl)imizazol-5-ylcarbonylamino)azepin-1-yl)propionicacid instead of2-(hexahydro-2-oxo-3S-(thiazol-4-ylcarbonylamino)azepin-1-yl)propionicacid, the compound of the present invention having the followingphysical data was obtained.

TLC:Rf 0.63 (chloroform:methanol=9:1); NMR (DMSO-d₆): δ 8.87-8.53 (2H,m), 8.29-8.17 (1H, m), 7.87-7.75 (2H, m), 7.27 (5H, m), 5.67 (2H, m),5.37 (2H, m), 5.26-4.62 (3H, m), 4.13 (2H, m), 3.48 (2H, t, J=7.7 Hz),3.28 (2H, m), 2.80 (1H, m), 2.57 (1H, m), 2.02-1.45 (6H, m), 1.38 (9H,s), 1.32 (3H, m), 0.84 (2H, t, J=7.7 Hz), −0.04 (9H, s).

EXAMPLE 21 (1)3-(N-(2-(hexahydro-2-oxo-3S-(imizazol-5-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid

By the same procedure as provided in example 6(1), using the compoundprepared in reference example 10, the compound of the present inventionhaving the following physical data was obtained.

TLC:Rf 0.69 (chloroform:methanol:water=6:4:1); NMR (DMSO-d₆): δ 12.53(1H, brs), 8.78-8.53 (1H, m), 8.30-8.16 (1H, m), 7.71-7.60 (2H, m), 7.28(5H, m), 5.67 (2H, m), 5.25-4.60 (3H, m), 4.14 (2H, m), 3.35 (2H, m),2.85-2.60 (2H, m), 2.04-1.40 (6H, m), 1.32 (3H, m).

EXAMPLE 22(1) AND EXAMPLE 22(2)

By the same procedure as provided in example 1, using5-(2,6-dichlorophenylmethyl)tetrazole andN-t-butoxycarbonyl-3-amino-4-oxo-5-bromopentanoic acid.ethylesterinstead ofN-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-bromopentanoicacid.t-butylester, the compounds of the present invention having thefollowing physical data were obtained.

EXAMPLE 22(1)N-t-butoxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid.ethylester

TLC:Rf 0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.35 (1H, d,J=8.8 Hz), 7.34 (1H, d, J=7.6 Hz), 7.16 (1H, dd, J=8.8 Hz, 7.6 Hz), 5.82and 5.61 (each 1H, d, J=17.8 Hz), 5.72-5.59 (1H, m), 4.68-4.53 (1H, m),4.61 (2H, s), 4.15 (2H, q, J=7.2 Hz), 3.06 (1H, dd, J=17.5 Hz, 5.0 Hz),2.76 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.47 (9H, s), 1.25 (3H, t, J=7.2 Hz).

EXAMPLE 22(2)N-t-butoxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.ethylester

TLC:Rf 0.23 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.37 (1H, d,J=8.8 Hz), 7.37 (1H, d, J=7.2 Hz), 7.21 (1H, dd, J=8.8 Hz, 7.2 Hz), 5.74and 5.57 (each 1H, d, J=18.6 Hz), 5.66-5.52 (1H, m), 4.65-4.50 (1H, m),4.39 and 4.29 (each 1H, d, J=17.5 Hz), 4.17 (2H, q, J=7.0 Hz), 3.13 (1H,dd, J=17.5 Hz, 5.0 Hz), 2.83 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.50 (9H, s),1.27 (3H, t, J=7.0 Hz).

EXAMPLE 23(1)N-t-butoxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid

To a solution of the compound prepared in example 22(1) (72 mg) in1,2-dimethoxyethane (0.5 ml) was added 1 N aqueous solution of sodiumhydroxide (0.15 ml) at 0° C. The reaction mixture was stirred for 30 minat 0° C. The mixture was quenched by addition of 1 N aqueous solution ohhydrochloric acid, extracted with ethyl acetate. The extract was washedwith a saturated aqueous solution of sodium chloride, dried overanhydrous sodium sulfate, concentrated to give the compound of thepresent invention (62 mg) having the following physical data.

TLC:Rf 0.49 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.57-7.30 (4H, m), 5.95-5.74 (2H, m), 4.51 (2H, s), 4.58-4.40 (1H, m),2.82-2.39 (2H, m), 1.40 (9H, s).

EXAMPLE 23(2)N-t-butoxycarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

By the same procedure as provided in example 23(1), using the compoundprepared in example 22(2), the compound of the present invention havingthe following physical data was obtained.

TLC:Rf 0.37 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.68-7.33 (4H, m), 5.92-5.77 (2H, m), 4.60-4.43 (1H, m), 4.34 (2H, s),2.86-2.58 (2H, m), 1.41 (9H, s).

REFERENCE EXAMPLE 11 (1)3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester.hydrochloric acid salt

To the compound prepared in example 22(1) (201 mg) was added 4Nhydrochloric acid in dioxane (4 ml). The reaction mixture was stirredfor 30 min at room temperature. The mixture was concentrated. Theresidue was removed as toluene azeotrope. The obtained residue waswashed with ether, to give the title compound (150 mg) having thefollowing physical data.

TLC:Rf 0.28 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 8.60-8.20 (3H,br), 7.62 (1H, d, J=9.0 Hz), 7.62 (1H, d, J=6.8 Hz), 7.37 (1H, dd, J=9.0Hz, 6.8 Hz), 6.21 and 6.02 (each 1H, d, J=18.0 Hz), 4.65-4.55 (1H, m),4.54 (2H, s), 4.12 (2H, q, J=7.0 Hz), 3.35-3.03 (2H, m), 1.20 (3H, t,J=7.0 Hz).

REFERENCE EXAMPLE 11(2)3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.ethylester.hydrochloric acid salt

By the same procedure as provided in reference example 11(1), using thecompound prepared in example 22(2), the title compound having thefollowing physical data was obtained.

TLC:Rf 0.33 (chloroform:methanol=19:1).

REFERENCE EXAMPLE 11(3)3-amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.ethylester.hydrochloric acid salt

By the same procedure as provided in example 1→reference example 11(1),using 5-phenylmethyltetrazole andN-t-butoxycarbonyl-3-amino-4-oxo-5-bromopentanoic acid.ethylesterinstead ofN-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-bromopentanoicacid.t-butylester, the title compound having the following physical datawas obtained.

TLC:Rf 0.50 (chloroform:methanol=9:1).

EXAMPLE 24(1)-24(12)

By the same procedure as provided in example 18(1), using thecorresponding carboxylic acid compounds and the compound prepared inreference example 11(1), reference example 11(2) or reference example11(3) instead of the compound prepared in reference example 9(1), thecompounds of the present invention having the following physical datawere obtained.

EXAMPLE 24(1)N-(N-benzyloxycarbonyl-L-alanyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.43 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.50-7.07 (9H,m), 5.82-5.61 and 5.61-5.39 (2H, m), 5.36 and 5.25 (total 1H, each d,J=5.5 Hz), 5.10 and 5.08 (total 2H, each s), 4.98-4.82 (1H, m), 4.59(2H, s), 4.33-4.13 (1H, m), 4.12 (2H, q, J=7.0 Hz), 3.10-2.85 and2.81-2.59 (total 2H, m), 1.41 and 1.40 (total 3H, each d, J=7.0 Hz),1.23 (3H, t, J=7.0 Hz).

EXAMPLE 24(2)N-(N-benzyloxycarbonyl-L-alanyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.ethylester

NMR (CDCl₃): δ 7.50-7.10 (8H, m), 5.85-5.60 and 5.60-5.28 (2H, m),5.25-5.00 (2H, m), 4.90-4.77 (1H, m), 4.35-4.07 (5H, m), 3.19-2.99 and2.87-2.79 (2H, m), 1.52-1.38 (3H, m), 1.27 (3H, t, J=7.0 Hz).

EXAMPLE 24(3)N-(N-benzyloxycarbonyl-L-valyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.20 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 8.92-8.79 and8.72-8.60 (2H, m), 7.61-7.44 and 7.44-7.15 (8H, m), 5.84 (2H, m),4.80-4.62 (1H, m)4.51 (2H, s), 4.04 (2H, q, J=7.0 Hz), 3.93 (1H, m),3.00-2.55 (2H, m), 2.08-1.92 (1H, m), 1.16 (3H, t, J=7.0 Hz), 0.96-0.75(6H, m).

EXAMPLE 24(4)N-(N-benzyloxycarbonyl-N′-t-butyloxycarbonyl-L-lysinyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.47 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 8.88-8.75 and8.72-8.60 (total 1H, m), 7.63-7.45 and7.45-7.10 (9H, m), 6.82-6.68(total 1H, m), 5.96-5.72 (2H, m), 4.99 (2H, s), 4.93-4.60 (1H, m), 4.51(2H, s), 4.15-3.85 (1H, m), 4.05 (2H, q, J=6.8 Hz), 2.96-2.55 (2H, m),1.68-1.05 (6H, m), 1.36 (9H, s), 1.16 (3H, t, J=6.8 Hz).

EXAMPLE 24(5)N-phenylcarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid.ethylester

TLC:Rf 0.54 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 9.07 (1H, d,J=9.5 Hz), 7.95-7.84 and 7.63-7.25 (8H, m), 5.94 (2H, s), 5.08-4.94 (1H,m), 4.50 (2H, s), 4.06 (2H, q, J=7.2 Hz), 2.96 (1H, dd, J=16.0 Hz, 5.5Hz), 2.74 (1H, dd, J=116.0 Hz, 7.5 Hz), 1.15 (3H, t, J=7.0 Hz).

EXAMPLE 24(6)N-(2-phenylethylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.24 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.43-6.97 (8H,m), 6.57 (1H, d, J=9.5 Hz), 5.21 and 5.09 (each 1H, d, J=18.0 Hz),4.94-4.76 (1H, m), 4.59 (2H, s), 4.10 (2H, q, J=7.0 Hz), 3.10-2.85 and2.79-2.45 (6H, m), 1.23 (3H, t, J=7.0 Hz).

EXAMPLE 24(7)N-phenyloxymethylcarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.52 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.80-7.66 (1H,m), 7.42-6.87 (8H, m), 5.63 and 5.52 (each 1H, d, J=18.0 Hz), 5.07-4.92(1H, m), 4.60 (4H, s), 4.13 (2H, q, J=7.0 Hz), 3.07 (1H, dd, J 17.5 Hz,4.5 Hz), 2.74 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.24 (3H, t, J=7.0 Hz).

EXAMPLE 24(8)N-(2-(hexahydro-2-oxo-azepin-1-yl)propionyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.ethylester

TLC:Rf 0.47 (ethyl acetate); NMR (CDCl₃): δ 7.50-7.15 (3H, m), 5.80-5.42(2H, m), 5.08-4.91 (1H, m), 4.91-4.74 (1H, m), 4.36 and 4.35 (total 2H,each s), 4.22-4.11 (2H, m), 3.46-3.22 (2H, m), 3.11-2.68 (2H, m),2.69-2.44 (2H, m), 1.98-1.39 (6H, m), 1.63 (9H, s), 1.48-1.34 (3H, m),1.27 (3H, t, J=7.2 Hz).

EXAMPLE 24(9)N-(2S-(tetrahydro-5-oxo-1,4-benzooxsazepin-4-yl)propionyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.ethylester

TLC: Hf 0.12 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.85-6.93 (8H,m), 5.84-5.40 (2H, m), 5.35-5.11 (1H, m), 4.98-4.75 (1H, m), 4.51-3.96(6H, m), 3.72-3.42 (2H, m), 3.25-2.69 (2H, m), 1.71-1.40 (2H, m),1.40-1.02 (3H, m).

EXAMPLE 24(10)N-(2S-(2,3-indol-3,4-tetrahydro-2-oxoazepin-1-yl)propionyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.ethylester

TLC:Rf 0.16 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 11.18 (1H, s),8.90-8.69 (1H, m), 7.62-6.89 (1H, m), 5.87 (2H, m), 5.38-5.16 (1H, m),4.98-4.79 (1H, m) 4.46-4.17 (2H, m), 4.17-3.95 (2H, m), 3.65-2.63 (6H,m), 2.42-1.85 (2H, m), 1.50-1.30 (3H, m), 1.30-0.98 (3H, m).

EXAMPLE 24(11)N-(2-(4-fluorophenyl)-4-oxo-5-benzyloxocarbonylaminopyrimidin-3-yl)methylcarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.ethylester

TLC:Rf 0.56 (chloroform:methanol=10:1); NMR (CDCl₃): δ 8.77 (1H, brs),7.70-7.07 (14H, m), 5.90 and 5.52 (each 1H, each d, J=18.5 Hz), 5.18(2H, s), 4.91 (1H, m), 4.60 and 4.52 (each 1H, each d, J=15.0 Hz), 4.31(2H, s), 4.11 (2H, q, J=7.0 Hz), 3.06 and 2.82 (each 1H, each dd,J=16.0, 5.0 Hz), 1.22 (3H, t, J=7.0 Hz).

EXAMPLE 24(12)3-(N-(2-(hexahydro-2-oxo-3S-(quinolin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid.ethylester

TLC:Rf 0.65 (chloroform:methanol=9:1); NMR (CDCl₃): δ 9.31-9.22 (1H, m),9.13 (1H, m), 8.54 (1H, m), 8.02 (2H, m), 7.73 (2H, m), 7.48 (1H, m),7.32-7.21 (5H, m), 5.60-5.25 (2H, m), 4.97-4.73 (3H, m), 4.24-4.06 (4H,m), 3.55 (2H, m), 3.05-2.72 (2H, m), 2.27-1.84 (6H, m), 1.44 (3H, d,J=7.0 Hz), 1.30-1.18 (3H, m).

EXAMPLE 25(1)-25(11)

By the same procedure as provided in example 23(1), using the compoundprepared in example 24(1)-24(11), the compounds of the present inventionhaving the following physical data were obtained.

EXAMPLE 25(1)N-(N-benzyloxycarbonyl-L-alanyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.29 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.64-12.25 (1H, m), 8.79-8.56 (1H, m), 7.66-7.55 (1H, m), 7.55-7.45 and7.45-7.12 (8H, m), 6.00-5.55 (2H, m), 5.00 (2H, s), 4.81-4.57 (1H, m),4.51 (2H, s), 4.14-4.00 (1H, m), 2.86-2.35 (2H, m), 1.23 and 1.21 (total3H, each d, J=7.4 Hz).

EXAMPLE 25(2)N-(N-benzyloxycarbonyl-L-alanyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.63-12.35 (1H, m), 9.00-8.72 (1H, m), 7.70-7.20 (9H, m), 5.87-5.73(2H, m), 5.06-4.87 (2H, s), 4.87-4.60 (1H, m), 4.36-4.22 (2H, s),4.22-3.95 (1H, m), 2.90-2.55 (2H, m), 1.30-1.05 (3H, m).

EXAMPLE 25(3)N-(N-benzyloxycarbonyl-L-valyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.61 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.65-12.25 (1H, br), 8.86-8.55 (1H, m), 7.59-7.15 (9H, m), 6.02-5.50(2H, m), 5.00 (2H, s), 4.88-4.58 (1H, m), 4.51 (2H, s), 3.93-3.77 (1H,m), 2.92-2.22 (2H, m), 2.06-1.93 (1H, m), 0.95-0.76 (6H, m).

EXAMPLE 25(4)N-(N-benzyloxycarbonyl-N′-t-butyloxycarbonyl-L-lysinyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.38 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.72-8.55 (1H, m), 7.61-7.43 (3H, m), 7.43-7.05 (6H, m), 6.81-6.70 (1H,m), 5.92-5.53 (2H, m), 4.99 (2H, s), 4.72-4.55 (1H, m), 4.50 (2H, s),4.04-3.87 (1H, m), 2.96-2.79 (4H, m), 2.72-2.56 (2H, m), 1.71-1.12 (15H,m).

EXAMPLE 25(5) N-phenylcarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl) tetrazol-2-yl)pentanoic acid

TLC:Rf 0.48 (chloroform:methanol:acetic acid=18:1:1); NMR (CDCl₃): δ612.60-12.25 (1H, br), 9.12-9.00 (1H, m), 7.95-7.86 (2H, m), 7.65-7.10(6H, m), 6.00-5.87 (2H, m), 5.02-4.89 (1H, m), 4.50 (2H, s), 3.00-2.80and 2.80-2.58 (2H, m).

EXAMPLE 25(6)N-(2-phenylethylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.50 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.65-12.30 (1H, br), 8.65-8.52 (1H, m), 7.53 (2H, dd, J=9.0, 7.4 Hz),7.34 (1H, dd, J=9.0, 7.4 Hz), 7.29-7.00 (6H, m), 5.68-5.52 (2H, m),4.74-4.58 (1H, m), 4.51 (2H, s), 2.93-2.40 (6H, m).

EXAMPLE 25(7)N-phenyloxymethylcarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.61 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ12.62-12.30 (1H, br), 8.77-7.66 (1H, m), 7.52 (2H, d, J=7.5 Hz),7.44-7.22 (4H, m), 7.02-6.88 (3H, m), 5.91-5.75 (2H, m), 5.00-4.81 (1H,m), 4.61 (2H, s), 4.51 (2H, s), 2.92-2.56 (2H, m).

EXAMPLE 25(8)N-(2-(hexahydro-2-oxo-azepin-1-yl)propionyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.09-11.98 (1H, br), 8.74-8.43 (1H, m), 7.60-7.29 (3H, m), 5.83 (2H,brs), 5.06-4.86 (1H, m), 4.85-4.62 (1H, m), 4.34 (2H, s), 3.35 (2H,brs), 2.97-2.56 (2H, m), 2.47 (2H, brs), 1.95-1.30 (6H, m), 1.27 (3H, d,J=7.2 Hz).

EXAMPLE 25(9) N-(2S-(tetrahydro-5-oxo-1,4-benzooxsazepin-4-yl)propionyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.42 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.98-12.14 (1H, br), 9.12-8.70 (1H, m), 7.75-7.26 (5H, m), 7.10-6.86(2H, m), 6.07-5.63 (2H, brs), 5.28-4.96 (1H, m), 4.96-4.60 (1H, m),4.52-4.12 (4H, m), 3.76-3.42 (2H, m), 3.03-2.55 (2H, m), 1.44 (3H, d,J=7.2 Hz).

EXAMPLE 25(10)N-(2S-(2,3-indol-3,4-tetrahydro-2-oxoazepin-1-yl)propionyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.30 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.90-12.16 (1H, br), 11.18 (1H, s), 8.97-8.64 (1H, m), 7.68-6.86 (7H,m), 5.88 (1H, brs), 5.43-5.10 (1H, m), 4.98-4.62 (1H, m), 4.49-4.12 (1H,m), 3.70-3.35 (2H, m), 3.15-2.53 (4H, m), 2.36-1.82 (2H, m), 1.55-1.20(3H, m).

EXAMPLE 25(11)N-(2-(4-fluorophenyl)-4-oxo-5-benzyloxocarbonylaminopyrimidin-3-yl)methylcarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid

TLC:Rf 0.31 (chloroform:methanol=4:1); NMR (DMSO-d₆): δ 9.21 (1H, m),8.86 (1H, brs), 8.48 (1H, s), 7.70-7.20 (12H, m), 5.82 (2H, br), 5.12(2H, s), 4.78 (1H, m), 4,.58 (2H, brs), 4.27 (2H, brs), 2.80 (2H, m).

EXAMPLE 26(1) AND EXAMPLE 26(2)

By the same procedure as provided in reference example 11(1) and ifnecessary, by known methods converted to accommodate the correspondingsalts, using the compounds prepared in example 24(4) or example 25(4),the compounds of the present invention having the following physicaldata were obtained.

EXAMPLE 26(1)N-(N-benzyloxycarbonyl-L-lysinyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester.hydrochloric acid salt

TLC:Rf 0.38 (chloroform:methanol:acetic acid=8:1:1); NMR (DMSO-d₆): δ8.90-8.79 and 8.79-8.66 (1H, m), 7.92-7.65 (3H, br), 7.65-7.55 (1H, m),7.50 (2H, d, J=7.5 Hz), 7.43-7.10 (6H, m), 5.95-5.53 (3H, m), 5.00 (2H,s), 4.91-4.65 (1H, m), 4.51 (2H, s), 4.13-3.83 (3H, m), 2.93-2.55 (4H,m), 1.75-1.22 (6H, m), 1.16 (3H, t, J=7.2 Hz).

EXAMPLE 26(2)N-(N-benzyloxycarbonyl-L-lysinyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.11 (chloroform:methanol:water=70:30:3); NMR (DMSO-d₆): δ12.80-12.18 (1H, br), 8.87-8.65 (1H, m), 8.10-7.70 (3H, m), 7.70-7.45(3H, m), 7.45-7.12 (6H, m), 5.99-5.50 (2H, m), 5.00 (2H, s), 4.84-4.59(1H, m), 4.51 (2H, s), 4.07-3.87 (1H, m), 2.90-2.55 (4H, m), 1.72-1.19(6H, m).

EXAMPLE 27(1)-27(9)

By the same procedure as provided in example 1, using the correspondingtetrazole compounds and the corresponding bromo compounds instead ofN-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo-5-bromopentanoicacid.t-butylester, compounds of the present invention having thefollowing physical data were obtained.

EXAMPLE 27(1)N-(2-methylbenzyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.40-7.09 (7H,m), 6.02-5.86 (1H, m), 5.78 and 5.60 (each 1H, d, J=18.0 Hz), 5.18 (2H,s), 4.76-4.62 (1H, m), 4.59 (2H, s), 4.12 (2H, q, J=7.0 Hz), 3.06 (1H,dd, J=17.5 Hz, 5.0 Hz), 2.77 (1H, dd, J=17.5 Hz, 5.0 Hz), 2.35 (3H, s),1.23 (3H, t, J=7.0 Hz).

EXAMPLE 27(2)N-(pyridin-4-ylmethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.40 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 8.55 (2H, d,J=5.8 Hz), 8.12 (1H, d, J=9.5 Hz), 7.57-7.28 (3H, m), 7.34 (2H, d, J=5.8Hz), 5.96 (each 1H, s), 5.14 (2H, s), 4.76-4.60 (1H, m), 4.52 (2H, s),4.06 (2H, q, J=7.2 Hz), 2.86 (1H, dd, J=17.5 Hz, 5.0 Hz), 2.70 (1H, dd,J=17.5 Hz, 6.0 Hz), 2.35 (3H, s), 1.16 (3H, t, J=7.2 Hz).

EXAMPLE 27(3)N-(tetrahydrofuran-3-yloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.33 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.34 (1H, d,J=8.8 Hz), 7.34 (1H, d, J=7.6 Hz), 7.18 (1H, dd, J=8.8 Hz, 7.6 Hz), 5.95(1H, d, J=9.5 Hz), 5.80 and 5.62 (each 1H, d, J=18.0 Hz), 5.41-5.19 (1H,m), 4.73-4.52 (1H, m), 4.60 (2H, s), 4.15 (2H, q, J=7.0 Hz), 4.02-3.75(4H, m), 3.15-2.98 and 2.78-2.69 (2H, m), 2.32-1.92 (2H, s), 1.25 (3H,t, J=7.0 Hz).

EXAMPLE 27(4)N-(3-chlorobenzyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.71 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.45-7.10 (7H,m), 6.01-5.86 (11H, m), 5.78 and 5.61 (each 1H, d, J=18.0 Hz), 5.12 (2H,s), 4.74-4.55 (1H, m), 4.60 (2H, s), 4.15 (2H, q, J=7.2 Hz), 3.08 (1H,dd, J=17.5 Hz, 4.5 Hz), 2.76 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.24 (3H, t,J=7.2 Hz).

EXAMPLE 27(5)N-(2-propenoxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.33 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.26 (1H, d,J=8.6 Hz), 7.26 (1H, d, J=7.4 Hz), 7.09 (1H, dd, J=8.6 Hz, 7.4 Hz),6.00-5.73 (2H, m), 5.75 and 5.56 (each 1H, d, J=18.0 Hz), 5.25 (1H, dd,J=17.2 Hz, 1.0 Hz), 5.18 (1H, dd, J=11.2 Hz, 1.0 Hz), 4.68-4.45 (1H, m),4.54 (2H, s), 4.52 (2H, s), 4.06 (2H, q, J=7.0 Hz), 2.98 (1H, dd, J=17.5Hz, 4.5 Hz), 2.72 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.16 (3H, t, J=7.0 Hz).

EXAMPLE 27(6)N-(naphthalen-2-ylmethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.92-7.75 and7.56-7.41 (7H, m), 7.34 (1H, d, J=8.8 Hz), 7.33 (1H, d, J=7.6 Hz), 7.18(1H, dd, J=8.8 Hz, 7.6 Hz), 6.02-5.87 (1H, m), 5.78 and 5.59 (each 1H,d, J=18.0 Hz), 5.32 (2H, s), 4.72-4.50 (1H, m), 4.60 (2H, s), 2.99 (1H,dd, J=17.5 Hz, 4.5 Hz), 2.72 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.40 (9H, s).

EXAMPLE 27(7)N-(naphthalen-1-ylmethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.44 (hexane:ethyl acetate=2:1);

NMR (CDCl₃): δ 8.11-7.98, 7.95-7.81 and 7.63-7.40 (7H, m), 7.34 (1H, d,J=9.0 Hz), 7.34 (1H, d, J=7.0 Hz), 7.18 (1H, dd, J=9.0 Hz, 7.0 Hz),5.96-5.85 (1H, m), 5.76 (1H, d, J=18.0 Hz), 5.64 (2H, s), 5.58 (1H, d,J=18.0 Hz) 4.72-5.85 (1H, m), 4.6 0 (2H, s), 2.9 9 (1H, dd, J=17.5 Hz,4.0 Hz), 2.68 (1H, dd, J=17.5 Hz, 4.5 Hz), 1.38 (9H, s).

EXAMPLE 27(8)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.ethylester

TLC:Rf 0.63 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.48-7.42 (2H,m), 7.34-7.14 (6H, m), 6.56 (1H, d, J=8.4 Hz), 5.67 (1H, d, J=17.8 Hz),5.46 (1H, d, J=17.8 Hz), 4.87 (1H, m), 4.15 (2H, q, J=7.2 Hz), 3.23 (2H,m), 3.08 (1H, dd, J=17.4 Hz, 4.4 Hz), 2.93 (2H, m), 2.74 (1H, dd, J=17.4Hz, 4.8 Hz), 1.25 (3H, t, J=7.2 Hz).

EXAMPLE 27(9)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.ethylester

TLC:Rf 0.54 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.48-7.43 (2H,m), 7.37-7.17 (6H, m), 6.62 (1H, d, J=8.8 Hz), 5.61 (1H, d, J=18.6 Hz),5.40 (1H, d, J=18.6 Hz), 4.93 (1H, m), 4.18 (2H, q, J=7.2 Hz), 3.28 (2H,m), 3.16 (1H, dd, J=17.6 Hz, 4.4 Hz), 2.96 (2H, m), 2.79 (1H, dd, J=17.4Hz, 5.0 Hz), 1.28 (3H, t, J=7.2 Hz).

EXAMPLE 28(1-28(7)

By the same procedure as provided in example 23(1), using the compoundsprepared in example 27(1)-27(7), the compounds of the present inventionhaving the following physical data were obtained.

EXAMPLE 28(1)N-(2-methylbenzyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2yl)pentanoicacid

TLC:Rf 0.25 (chloroform:methanol=50:1); NMR (DMSO-d₆): δ 12.65-12.30(1H, br), 8.02-7.86 (1H, m), 7.51 (2H, d, J=7.5 Hz), 7.42-7.25 (2H, m),7.25-7.10 (3H, m), 5.98-5.83 (2H, m), 5.07 (2H, s), 4.67-4.53 (1H, m),4.50 (2H, s), 2.88-2.40 (2H, m), 2.28 (3H, s).

EXAMPLE 28(2)N-(pyrdin-4-ylmethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.46 (chloroform;methanol:acetic acid=8:1); NMR (DMSO-d₆): δ12.80-12.25 (1H, br), 8.70-8.45 (2H, m), 8.18-8.01 (1H, m), 7.53 (2H, d,J=7.0 Hz), 7.46-7.28 (3H, m), 6.10-5.80 (2H, m), 5.13 (2H, s), 4.70-4.56(1H, m), 4.51 (2H, s), 2.91-2.56 (2H, m).

EXAMPLE 28(3)N-(tetrahydrofuran-3-yloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.46 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.88-7.76 (1H, m), 7.52 (1H, d, J=8.8 Hz), 7.51 (1H, d, J=6.8 Hz), 7.37(1H, dd, J=8.8 Hz, 6.8 Hz), 5.95-5.78 (2H, m), 5.20-5.07 (1H, m),4.61-4.43 (1H, m), 4.50 (2H, s), 3.83-3.60 (4H, m), 2.87-2.20 (2H, m),2.33-2.00 and 2.00-1.80 (each 1H, m).

EXAMPLE 28(4)N-(3-chlorobenzyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.20 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ8.00-7.87 (1H, m), 7.60-7.27 (7H, m), 6.00-5.80 (2H, m), 5.07 (2H, s),4.67-4.42 (1H, m), 4.50 (2H, s), 2.86-2.54 (2H, m).

EXAMPLE 28(5)N-(2-propenoxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.22 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ12.53-12.30 (1H, m), 7.58 and 7.57 (total 2H, each d, J=8.4 Hz and 7.0Hz), 7.43 (1H, dd, J=8.4 Hz and 7.0 Hz), 6.10-5.84 (3H, m), 5.36 (1H,dd, J=17.4 Hz, 1.4 Hz), 5.25 (1H, dd, J=10.6 Hz, 1.4 Hz), 4.74-4.50 (1H,m), 4.58 (2H, d, J=5.2 Hz), 4.57 (2H, s), 2.93-2.52 (2H, m).

EXAMPLE 28(6)N-(naphthalen-2-ylmethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.26 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ8.08-7.81 (5H, m), 7.58-7.42 (5H, m), 7.36 (2H, d, J=9.0 Hz, 7.5 Hz),6.03-5.80 (2H, m), 5.25 (2H, s), 4.70-4.55 (1H, m), 4.52 (2H, s),2.91-2.53 (2H, m).

EXAMPLE 28(7)N-(naphthalen-1-ylmethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.63 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.12-7.84 and 7.65-7.26 (total 11H, m), 6.07-5.78 (2H, m), 5.56 (2H, s),4.70-4.55 (1H, m), 4.52 (2H, s), 2.90-2.55 (2H, m).

EXAMPLE 29(1)N-(4-t-butylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

To a solution of the compound prepared in reference example (725 mg) indichloromethane (5 ml) was added 4-t-butylbenzenesulfonyl cloride (524mg), triethylamine (0.2 ml) and dimethylaminopyridine (185 mg) at 0° C.,successively. The reaction mixture was stirred for 6 h for roomtemperature. The reaction mixture was quenched by addition of 1 Naqueous solution of hydrochloric acid, extracted with ethyl acetate. Theextract was washed with water and a saturated aqueous solution of sodiumchloride, successively, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl:acetate=3:1) to give the compound of thepresent invention (526 mg)-having the following physical data.

TLC:Rf 0.46 (hexane:ethyl acetate=2:1); NMR (DMSO-d₅): δ 7.91-7.72 (2H,m), 7.68-7.50 (2H, m), 7.46-7.16 (3H, m), 6.01 (1H, d, J=9.2 Hz), 5.76(1H, d, J=18.8 Hz), 5.63 (1H, d, J=18.8 Hz), 4.29 (2H, s), 4.21-4.02(1H, m), 2.96 (1H, dd, J=17.6 and 4.2 Hz), 2.40 (1H, dd, J=17.6 and 4.4Hz), 1.37 (9H, s), 1.36 (9H, s).

EXAMPLE 29(2)-29(74)

By the same procedure as provided in example 29(1), using the compoundsprepared in reference example 9(1) or reference example 9(2) and thecorresponding sulfonyl chloride compounds, the compounds of the presentinvention having the following physical data were obtained.

EXAMPLE 29(2)N-phenylmethylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.77 (chloroform:methanol=19:1); NMR (DMSO-d₆): δ 7.90 (1H, d,J=9.0 Hz), 7.58-7.29 (8H, m), 5.98 (2H, m), 4.52 (4H, m), 2.77-2.64 (2H,m), 1.38 (9H, s).

EXAMPLE 29(3)N-phenylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.57 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.93-7.83 and7.71-7.48 (5H, m), 7.35 (1H, d, J=9.0 Hz), 7.35 (1H, d, J=7.0 Hz), 7.18(1H, dd, J=9.0 Hz, 7.0 Hz), 6.07 (1H, d, J=9.5 Hz), 5.83 and 5.62 (each1H, d, J=18.0 Hz), 4.59 (2H, s), 4.20-4.05 (1H, m), 2.82 (1H, dd, J=7.5Hz, 4.0 Hz), 2.24 (1H, dd, J=17.5 Hz, 4.5 Hz), 1.37 (9H, s).

EXAMPLE 29(4)N-(2-(naphthalen-1-yl)ethyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.11-7.73 and7.63-7.08 (10H, m), 5.72 and 5.58 (each 1H, d, J=18.0 Hz), 4.58 (2H, s),4.32-4.19 (1H, m), 3.74-3.55 and 3.53-3.37 (total 4H, m), 2.91 (1H, dd,J=17.5 Hz, 4.5 Hz), 2.52 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.38 (9H, s).

EXAMPLE 29(5)N-(naphthalen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.24 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 8.45 (1H, m),8.07-7.59 (6H, m), 7.34 (1H, d, J=9.0 Hz), 7.34 (1H, d, J=7.0 Hz), 7.17(1H, dd, J=9.0 Hz, 7.0 Hz), 6.20 (1H, d, J=9.5 Hz), 5.88 and 5.67 (each1H, d, J=18.0 Hz), 4.58 (2H, s), 4.26 (1H, m), 2.79 (1H, dd, J=17.5 Hz,4.0 Hz), 2.20 (1H, dd, J=17.5 Hz, 4.5 Hz), 1.33 (9H, s).

EXAMPLE 29(6)N-(naphthalen-1-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.21 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 8.62-8.50,8.35-8.26, 8.18-8.07, 8.05-7.94 and 7.76-7.46 (7H, m), 7.33 (1H, d,J=9.0 Hz), 7.33 (1H, d, J=7.0 Hz), 7.16 (1H, dd, J=9.0 Hz, 7.0 Hz),6.50-6.39 (1H, m), 5.84 and 5.56 (each 1H, d, J=18.0 Hz), 4.57 (2H, s),4.12-3.95 (1H, m), 2.65 (1H, dd, J=17.5 Hz, 4.0 Hz), 1.78 (1H, dd,J=17.5 Hz, 5.0 Hz), 1.24 (9H, s).

EXAMPLE 29(7)N-(2-phenylethenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.53 (hexane:ethyl acetate=3:1); NMR (DMSO-d₆): δ 7.55 (1H, d,J=15.6 Hz), 7.52-7.40 (5H, m), 7.36-7.17 (3H, m), 6.77 (1H, d, J=15.6Hz), 5.92 (1H, d, J=18.2 Hz), 5.73 (1H, d, J=18.2 Hz), 4.59 (2H, s),4.20 (1H, m), 2.98 (1H, dd, J=17.4, 4.2 Hz), 2.70 (1H, dd, J=17.4, 4.2Hz), 1.39 (9H, s).

EXAMPLE 29(8)N-(4-bromophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.44 (hexane:ethyl acetate=2:1); NMR (DMSO-d₆): δ 7.76 and 7.66(each 2H, d, J=8.5 Hz), 7.34 (1H, d, J=9.0 Hz), 7.34 (1H, d, J=7.0 Hz),7.16 (1H, dd, J=9.0 Hz, 7.0 Hz), 6.12 (1H, J=9.6 Hz), 5.84 and 5.64(each 1H, d, J=118.0 Hz), 4.60 (2H, s), 4.19-4.03 (1H, m), 2.82 (1H, dd,J=17.8 Hz, 3.8 Hz), 2.31 (1H, dd, J=17.8 Hz, 4.6 Hz), 1.38 (9H, s).

EXAMPLE 29(9)N-butylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid.t-butylester

TLC:Rf 0.60 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.37-7.24 (3H,m), 5.89 (2H, d, J=17.2 Hz), 5.74 (1H, d, J=17.2 Hz), 4.61 (1H, s),4.38-4.28 (1H, m), 3.12-3.02 (2H, m), 2.98 (1H, dd, J=17.0, 4.6 Hz),2.74 (1H, dd, J=17.0, 4.6 Hz), 1.91-1.79 (2H, m), 1.63-1.61 (2H, m),1.43 (9H, s), 0.96 (3H, t, J=7.2 Hz).

EXAMPLE 29(10)N-(quinolin-8-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.46 (hexane:ethyl:acetate=1:1); NMR (CDCl₃): δ 9.02 (1H, dd,J=4.3, 1.7 Hz), 8.47-8.10 (3H, m), 7.73-7.55 (2H, m), 7.44 (1H, d, J=7.5Hz), 7.37-7.13 (4H, m), 6.02 (1H, d, J=16.6 Hz), 5.87 (1H, d, J=16.6Hz), 4.60 (2H, s), 4.48-4.41 (1H, m), 2.66 (1H, dd, J=17.0, 4.5 Hz),2.96 (1H, dd, J=17.0, 4.5 Hz), 1.27 (9H, s).

EXAMPLE 29(11)N-(5-dimethylaminonaphthalen-1-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.58 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 8.60 (1H, d,J=8.5 Hz), 8.31-8.19 (2H, m), 7.63-7.52 (2H, m), 7.36-7.13 (5H, m), 6.39(1H, d, J=9.9 Hz), 5.84 (1H, d, J=18.2 Hz), 5.55 (1H, d, J=18.2 Hz),4.58 (2H, s), 4.05-3.96 (1H, m), 2.89 (6H, s), 2.66 (1H, dd, J=17.2, 4.5Hz), 1.79 (1H, dd, J=17.2, 4.5 Hz), 1.25 (9H, s).

EXAMPLE 29(12)N-(4-nitrophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.60 (chloroform:methanol=19:1); NMR (CDCl₃): δ 8.38 and 8.05(each 2H, d, J=9.2 Hz), 7.36 (1H, d, J=8.8 Hz), 7.36 (1H, d, J=7.2 Hz),7.20 (1H, dd, J=8.8 Hz, 7.2 Hz), 6.25 (1H, d, J=9.6 Hz), 5.71 and 5.56(each 1H, d, J=18.0 Hz), 4.61 (2H, s), 4.27-4.10 (1H, m), 2.92 (1H, dd,J=17.8 Hz, 4.0 Hz), 2.38 (1H, dd, J=17.8 Hz, 5.0 Hz), 1.38 (9H, s).

EXAMPLE 29(13)N-phenylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid.t-butylester

TLC:Rf 0.46 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 8.66 (1H, d,J=10.0 Hz), 7.94-7.89 (2H, m), 7.65-7.33 (6H, m), 6.04-5.79 (2H, m),4.53-4.42 (1H, m), 4.28 (2H, s), 2.65-2.61 (2H, m), 1.33 (9H, s).

EXAMPLE 29(14)N-(2-fluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.92 (1H, dt,J=1.8, 7.8 Hz), 7.70-7.59 (1H, m), 7.37-7.14 (5H, m), 6.28 (1H, d, J=9.4Hz), 5.92 (1H, d, J=18.0 Hz), 5.74 (1H, d, J=18.0 Hz), 4.60 (2H, s),4.30-4.21 (1H, m), 2.92 (2H, dd, J=17.6, 3.7 Hz), 2.34 (2H, dd, J=17.6,3.7 Hz), 1.40 (9H, s).

EXAMPLE 29(15)N-(4-fluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.46 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.93-7.86 (2H,m), 7.38-7.15 (5H, m), 6.08 (1H, d, J=8.5 Hz), 5.83 (1H, d, J=18.0 Hz),5.63 (1H, d, J=18.0 Hz), 4.60 (2H, s), 4.18-4.08 (1H, m), 2.82 (2H, dd,J=17.4, 3.9 Hz), 2.30 (2H, dd, J=17.4, 3.9 Hz), 1.38 (9H, s).

EXAMPLE 29(16)N-(3-fluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.62 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.72-7.46 and7.42-7.12 (7H, m), 6.23-6.10 (1H, m), 5.84 and 5.64 (each 1H, d, J=118.0Hz), 4.60 (2H, s), 4.22-4.07 (1H, m), 2.84 (1H, dd, J=17.5 Hz, 4.0 Hz),2.38 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.37 (9H, s).

EXAMPLE 29(17)N-(2-bromophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.24 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 8.20-8.08 (1H,m), 7.92-7.72 (1H, m), 7.60-7.40 (2H, m), 7.34 (1H, d, J=9.0 Hz), 7.34(1H, d, J=7.0 Hz), 7.18 (1H, dd, J=9.0 Hz, 7.0 Hz), 6.68 (1H, d, J=9.6Hz), 5.98 and 5.80 (each 1H, d, J=18.0 Hz), 4.60 (2H, s), 4.17-4.00 (1H,m), 2.88 (1H, dd, J=17.5 Hz, 4.0 Hz), 2.19 (1H, dd, J=17.5 Hz, 5.0 Hz),1.40 (9H, s).

EXAMPLE 29(18)N-(4-methoxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.38 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.81 (2H, d,J=9.0 Hz), 7.36-7.14 (3H, m), 7.01 (2H, d, J=9.0 Hz), 5.99 (1H, d, J=9.8Hz), 5.85 (1H, d, J=16.9 Hz), 5.63 (1H, d, J=16.9 Hz), 4.60 (2H, s),4.14-4.03 (1H, m), 2.81 (2H, dd, J=12.6, 3.7 Hz), 2.26 (2H, dd, J=12.6,3.7 Hz), 1.37 (9H, s).

EXAMPLE 29(19)N-(4-trifluoromethylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:1); NMR (DMSO-d₆): δ 8.01 (2H, d,J=8.8 Hz), 7.82 (2H, d, J=8.8 Hz), 7.37-7.15 (3H, m), 6.21 (1H, d, J=9.2Hz), 5.84 (1H, d, J=17.9 Hz), 5.65 (1H, d, J=17.9 Hz), 4.61 (2H, s),4.23-4.12 (1H, m), 2.81 (2H, dd, J=16.6, 4.0 Hz), 2.26 (2H, dd, J=16.6,4.0 Hz), 1.36 (9H, s).

EXAMPLE 29(20)N-(thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=2:1); NMR (DMSO-d₆): δ 7.68-7.65 (2H,m), 7.37-7.14 (3H, m), 7.13 (1H, t, J=4.4 Hz), 6.17 (1H, d, J=9.4 Hz),5.86 (1H, d, J=18.1 Hz), 5.66 (1H, d, J=18.1 Hz), 4.60 (2H, s),4.24-4.13 (1H, m), 2.89 (2H, dd, J=17.5, 3.7 Hz), 2.26 (2H, dd, J=17.5,3.7 Hz), 1.38 (9H, s).

EXAMPLE 29(21)N-(3-phenylpropyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.41 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.40-7.10 (8H,m), 5.82 and 5.66 (each 1H, d, J=18.0 Hz), 4.61 (2H, s), 4.32-4.16 (1H,m), 3.12-2.52 (6H, m), 2.30-2.50 (2H, m), 1.42 (9H, s).

EXAMPLE 29(22)N-(2-fluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

HPTLC:Rf 0.34 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.96 (1H, m),7.68 (1H, m), 7.46-7.10 (5H, m), 6.24 (1H, m), 5.84 and 5.75 (each 1H,each d, J=18.0 Hz), 4.30 (2H, s), 4.28 (1H, m), 3.05 and 2.45 (each 1H,each dd, J=17.5, 5.0 Hz), 1.40 (9H, s).

EXAMPLE 29(23)N-(4-chlorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.61 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.81 and 7.52(each 2H, d, J=8.0 Hz), 7.35 (1H, d, J=8.0 Hz), 7.35 (1H, d, J=8.2 Hz),7.19 (1H, dd, J=8.2 Hz, 7.0 Hz), 6.13 (1H, d, J=9.5 Hz), 5.84 and 5.64(each 1H, d, J=118.0 Hz), 4.60 (2H, s), 4.21-4.05 (1H, m), 2.83 (1H, dd,J=17.5 Hz, 4.5 Hz), 2.33 (1H, dd, J=7.5 Hz, 5.0 Hz), 1.37 (9H, s).

EXAMPLE 29(24)N-(3-chlorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.66 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.95-7.41 (4H,m), 7.34 (1H, d, J=9.0 Hz), 7.34 (1H, d, J=8.0 Hz), 7.18 (1H, dd, J=9.0Hz, 7.0 Hz), 6.17 (1H, d, J=9.6 Hz), 5.84 and 5.65 (each 1H, d, J=18.0Hz), 4.60 (2H, s), 4.23-4.08 (1H, m), 2.84 (1H, dd, J=17.6 Hz, 4.0 Hz),2.29 (1H, dd, J=17.6 Hz, 4.6 Hz), 1.38 (9H, s).

EXAMPLE 29(25)N-(2-chlorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.64 (chloroform:methanol=19:1); NMR (CDCl₃): δ 8.15-8.07 (1H,m), 7.61-7.40 (3H, m), 7.34 (1H, d, J=9.0 Hz), 7.34 (1H, d, J=7.0 Hz),7.17 (1H, dd, J=9.0 Hz, 7.0 Hz), 6.58 (1H, d, J=9.6 Hz), 5.97 and 5.79(each 1H, d, J=18.2 Hz), 4.60 (2H, s), 4.18-4.04 (1H, m), 2.88 (1H, dd,J=17.6 Hz, 3.6 Hz), 2.19 (1H, dd, J=17.6 Hz, 4.4 Hz), 1.40 (9H, s).

EXAMPLE 29(26)N-(2-phenyloxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.33 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 8.03-7.93,7.58-6.97 and 6.95-6.85 (1H, m), 6.38 (1H, d, J=9.6 Hz), 5.93 and 5.82(each 1H, d, J=18.0 Hz), 4.60 (2H, s), 4.38-4.22 (1H, m), 2.94 (1H, dd,J=17.5 Hz, 4.0 Hz), 2.46 (1H, dd, J=17.5 Hz, 5.0 Hz), 1.38 (9H, s).

EXAMPLE 29(27)N-(2-phenylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.45 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.14 (1H, dd,J=1.4, 7.8 Hz), 7.70-7.12 (11H, m), 5.67 (2H, s), 5.18 (1H, d, J=9.4Hz), 4.58 (2H, s), 3.96 (1H, m), 2.74 (1H, dd, J=4.0, 17 Hz), 2.25 (1H,d, J=4.8, 17 Hz), 1.36 (9H, s).

EXAMPLE 29(28)N-(3-phenylpropyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.28 (dichloromethane:ethyl acetate=20:1); NMR (CDCl₃): δ7.41-7.14 (8H, m), 5.78 and 5.68 (each 1H, d, J=19.0 Hz), 5.70 (1H, d,J=9.4 Hz), 4.35-4.19 (1H, m), 4.31 (2H, s), 3.19-2.95 and 2.87-2.60 (6H,m), 2.35-2.07 (2H, m), 1.43 (9H, s).

EXAMPLE 29(29)N-(2-methoxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.40 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.95-7.86 (1H,m), 7.63-7.46 (1H, m), 7.38-6.93 (5H, m), 6.38 (1H, d, J=8.5 Hz), 5.78(2H, s), 4.60 (2H, s), 4.30-4.12 (1H, m), 3.93 (3H, s), 2.85 (1H, dd,J=17.6 Hz, 4.0 Hz), 2.26 (1H, dd, J=17.6 Hz, 5.0 Hz), 1.40 (9H, s).

EXAMPLE 29(30)N-(2,6-difluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.33 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.65-7.46 (1H,m), 7.34 (1H, d, J=8.8 Hz), 7.34 (1H, d, J=7.2 Hz), 7.18 (1H, dd, J=8.8Hz, 7.2 Hz), 7.09 and 7.05 (each 1H, d, J=8.6 Hz), 6.56-6.45 (1H, m),5.91 and 5.75 (each 1H, d, J=18.0 Hz), 4.60 (2H, s), 4.45-4.53 (1H, m),2.98 (1H, dd, J=17.8 Hz, 3.6 Hz), 2.45 (1H, dd, J=17.8 Hz, 4.6 Hz), 1.41(9H, s).

EXAMPLE 29(31)N-(4-cyanophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.63 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.97 (2H, d,J=8.5 Hz), 7.83 (2H, d, J=8.5 Hz), 7.36 (2H, d, J=8.0 Hz), 7.19 (1H, t,J=8.0 Hz), 6.33-6.19 (1H, m), 5.81 and 5.61 (each 1H, d, J=18.0 Hz),4.61 (2H, s), 4.25-4.13 (1H, m), 2.80 (1H, dd, J=7.5 Hz, 4.0 Hz), 2.38(1H, dd, J=17.5 Hz, 4.6 Hz), 1.37 (9H, s).

EXAMPLE 29(32)N-(2-methylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.42 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 8.04-7.90 (1H,m), 7.58-7.19 (6H, m), 6.33-6.09 (1H, br), 5.81 (1H, dd, J=18.0 Hz),5.63 (1H, dd, J=18.0 Hz), 4.59 (2H, s), 4.14-3.97 (1H, m), 2.79 (1H, dd,J=17.6 and 3.6 Hz), 2.64 (3H, s), 2.18 (1H, dd, J=17.6 and 4.6 Hz), 1.38(9H, s).

EXAMPLE 29(33)N-(4-methylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.35 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.82-7.68 (2H,m), 7.44-7.10 (5H, m), 6.05 (1H, d, J=9.0 Hz), 5.86 (1H, dd, J=18.2 Hz),5.62 (I H, dd, J=18.2 Hz), 4.60 (2H, s), 4.22-4.02 (1H, m), 2.82 (1H,dd, J=17.6 and 3.8 Hz), 2.48 (3H, s), 2.26 (1H, dd, J=17.6 and 4.6 Hz),1.37 (9H, s).

EXAMPLE 29(34)N-(4-phenylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.26 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 8.00-7.86 (2H,m), 7.84-7.69 (2H, m), 7.67-7.38 (5H, m), 7.38-7.11 (3H, m, 6.14 (1H,brs), 5.87 (1H, d, J=18.2 Hz), 5.67 (1H, d, J=18.2 Hz), 4.59 (2H, s),4.27-4.06 (1H, m), 2.85 (1H, dd, J=17.4 and 4.0 Hz) 2.33 (1H, dd, J=17.4and 4.6 Hz), 1.37 (9H, s).

EXAMPLE 29(35)N-(5-dibutylaminonaphthalen-1-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.50 (hexane:ethyl:acetate=3:1); NMR (CDCl₃): δ 8.69 (1H, d,J=8.8 Hz), 8.37-8.14 (2H, m), 7.59-7.43 (2H, m), 7.43-7.06 (4H, m), 6.43(1H, d, J=10.0 Hz), 5.87 (1H, d, J=18.4 Hz), 5.57 (1H, d, J=18.4 Hz),4.58 (2H, s), 4.10-3.93 (1H, m), 3.11 (4H, t, J=7.2 Hz), 2.65 (1H, dd,J=17.8 and 3.4 Hz), 1.75 (1H, dd, J=17.8 and 4.6 Hz), 1.55-1.05 (8H, m),1.24 (9H, s), 0.83 (6H, t, J=7.0 Hz).

EXAMPLE 29(36)N-(3-phenylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.67 (chloroform:methanol=19:1); NMR (CDCl₃): δ 8.10 (1H, m),7.90-7.80 (2H, m), 7.67-7.39 (6H, m), 7.34 (1H, d, J=8.8 Hz), 7.34 (1H,d, J=7.0 Hz), 7.17 (1H, dd, J=8.8 Hz, 7.0 Hz), 6.24-6.11 (1H, m), 5.86and 5.67 (each 1H, d, J=18.0 Hz), 4.58 (2H, s), 4.25-4.12 (1H, m), 2.82(1H, dd, J=17.6 Hz, 4.0 Hz), 2.26 (1H, dd, J=17.6 Hz, 4.6 Hz), 1.33 (9H,s).

EXAMPLE 29(37)N-(4-acetylaminophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.47 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.80 (2H, d,J=9.2 Hz), 7.74-7.60 (1H, m), 7.69 (2H, d, J=9.2 Hz), 7.33 (1H, d, J=9.2Hz), 7.33 (1H, d, J=7.0 Hz), 7.17 (1H, dd, J=9.2 Hz, 7.0 Hz), 6.20-6.00(1H, m), 5.85 and 5.65 (each 1H, d, J=18.0 Hz), 4.59 (2H, s), 4.17-4.04(1H, m), 2.81 (1H, dd, J=17.4 Hz, 4.0 Hz), 2.21 (1H, dd, J=17.4 Hz, 4.8Hz), 1.35 (9H, s).

EXAMPLE 29(38)N-(4-t-butylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.23 (hexane:ethyl:acetate=3:1); NMR (CDCl₃): δ 7.86-7.72 (2H,m), 7.63-7.48 (2H, m), 7.42-7.10 (3H, m), 6.13-5.95 (1H, m, 5.84 (1H, d,J=18.0 Hz), 4.59 (2H, s), 4.22-4.01 (1H, m), 2.84 (1H, dd, J=17.6 and4.0 Hz), 2.27 (1H, dd, J=17.6 and 4.6 Hz), 1.36 (9H, s), 1.34 (9H, s).

EXAMPLE 29(39)N-(5-dimethylaminonaphthalen-1-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.29 (hexane:ethyl acetate=2:1); NMR (DMSO-d₆): δ 8.63 (1H, d,J=8.6 Hz), 8.30-8.12 (2H, m), 7.72-7.48 (2H, m), 7.48-7.10 (4H, m),6.42-6.20 (1H, br), 5.67 (1H, d, J=18.8 Hz), 5.46 (1H, d, J=18.8 Hz),4.32-3.87 (3H, m), 2.90 (6H, s), 2.81 (1H, dd, J=18.0 and 4.0 Hz), 2.01(1H, dd, J=18.0 and 4.0 Hz), 1.27 (9H, s).

EXAMPLE 29(40)N-(5-(pyridin-2-yl)thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.28 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.66-8.48 (1H,m), 7.88-7.66 (2H, m), 7.64 (1H, d, J=4.0 Hz), 7.51 (1H, d, J=4.0 Hz),7.43-7.06 (4H, m), 6.35-6.12 (1H, br), 5.92 (1H, d, J=18.2 Hz), 5.73(1H, d, J=18.2 Hz), 4.59 (2H, s), 4.31-4.15 (1H, m), 2.92 (1H, dd,J=17.2 and 3.4 Hz), 2.41 (1H, dd, J=17.2 and 4.4 Hz), 1.37 (9H, s).

EXAMPLE 29(41)N-(1-(3-chloro-5-trifluoromethylpyridin-2-yl)pyrrol-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.26 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 8.74-8.64 (1H,m), 8.21-8.11 (1H, m), 8.06 (1H, t, J=2.6 Hz), 7.56 (1H, t, J=2.2 Hz),7.44-7.04 (3H, m), 6.70-6.59 (1H, m), 6.07 (1H, d, J=9.4 Hz), 5.90 (1H,d, J=18.4 Hz), 5.71 (1H, d, J=18.4 Hz), 5.10 (2H, s), 4.28-4.04 (1H, m),2.92 (1H, dd, J=17.2 and 3.8 Hz), 2.50 (1H, dd, J=17.2 and 4.6 Hz), 1.39(9H, s).

EXAMPLE 29(42)N-(4-phenyloxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.42 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.85-7.75 and7.50-7.00 (12H, m), 6.03 (1H, d, J=9.6 Hz), 5.85 and 5.64 (each 1H, d,J=18.0 Hz), 4.60 (2H, s), 4.19-4.03 (1H, m), 2.85 (1H, dd, J=17.4 Hz,4.0 Hz), 2.33 (1H, dd, J=17.4 Hz, 4.6 Hz), 1.38 (9H, s).

EXAMPLE 29(43)N-(4-phenylthiophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.48 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.75-7.60 and7.60-7.12 (12H, m), 6.15-5.95 (1H, m), 5.84 and 5.62 (each 1H, d, J=18.0Hz), 4.60 (2H, s), 4.15-4.00 (1H, m), 2.82 (1H, dd, J=17.6 Hz, 4.0 Hz),2.30 (1H, dd, J=17.6 Hz, 4.6 Hz), 1.37 (9H, s).

EXAMPLE 29(44)N-octanylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.32 (hexane:ethyl:acetate=3:1); NMR (CDCl₃): δ 7.40-7.10 (3H,m), 5.89 (1H, d, J=i 7.8 Hz), 5.74 (1H, d, J=17.8 Hz), 4.61 (2H, s),4.44-4.24 (1H, m), 3.17-2.86 (3H, m), 2.74 (1H, dd, J=17.6 and 4.8 Hz),1.95-1.70 (2H, m), 1.58-1.14 (10H, m), 1.43 (9H, s), 0.88 (3H, t, J=7.5Hz).

EXAMPLE 29(45)N-(4-phenylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.17 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 8.06-7.89 (2H,m), 7.89-7.70 (2H, m), 7.70-7.16 (8H, m), 6.10 (1H, d, J=9.2 Hz), 5.80(1H, d, J=18.8 Hz), 5.68 (1H, d, J=18.8 Hz), 4.29 (2H, s), 4.27-4.09(1H, m), 2.98 (1H, dd, J=17.8 and 4.2 Hz), 2.44 (1H, dd, J=17.8 and 4.8Hz), 1.38 (9H, s).

EXAMPLE 29(46)N-(4-phenylcarbonylmethylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.79 (chloroform:methanol=19:1); NMR (CDCl₃): δ 68.06-7.93,7.90-7.75 and 7.70-7.10 (12H, m), 6.09 (1H, d, J=8.6 Hz), 5.83 and 5.69(each l H, d, J=18.0 Hz), 4.60 (2H, s), 4.39 (2H, s), 4.20-4.05 (1H, m),2.82 (1H, dd, J=17.6 Hz, 3.6 Hz), 2.27 (1H, dd, J=17.6 Hz, 4.6 Hz), 1.37(9H, s).

EXAMPLE 29(47)N-(2-acetylamino-4-methylthiazol-5-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.26 (chloroform:methanol=19:1); NMR (CDCl₃): δ 9.55-9.35 (1H,m), 7.34 (1H, d, J=9.0 Hz), 7.34 (1H, d, J=7.0 Hz), 7.17 (1H, dd, J=9.0Hz, 7.0 Hz), 6.40-6.26 (1H, m), 5.87 and 5.69 (each 1H, d, J=18.0 Hz),4.60 (2H, s), 4.31-4.15 (1H, m), 2.91 (1H, dd, J=17.6 Hz, 4.0 Hz), 2.52(3H, s), 2.35 (1H, dd, J=17.6 Hz, 4.4 Hz), 2.30 (3H, s), 1.39 (9H, s).

EXAMPLE 29(48)N-(2,2,2-trifluoroethylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.41 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.51 (1H, d,J=9.0 Hz), 7.51 (1H, d, J=7.0 Hz), 7.17 (1H, dd, J=9.0 Hz, 7.0 Hz), 6.27(1H, d, J=9.2 Hz), 5.91 and 5.72 (each 1H, d, J=18.0 Hz), 4.61 (2H, s),4.49-4.35 (1H, m), 4.19-4.82 (2H, m), 2.90-2.73 (2H, m), 1.43 (9H, s).

EXAMPLE 29(49)N-(2-trifluoromethylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.33 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.29-8.13 (1H,m), 8.00-7.84 (1H, m), 7.84-7.66 (2H, m), 7.41-7.10 (3H, m), 6.28 (1H,d, J=9.4 Hz), 5,91 (1H, d, J=18.0 Hz), 5.73)1H, d, J=18.0 Hz), 4.60 (2H,s), 4.25-4.08 (1H, m), 2.86 (1H, dd, J=17.6 and 3.6 Hz), 2.13 (1H, dd,J=17.6 and 4.8 Hz), 1.36 (9H, s).

EXAMPLE 29(50)N-(benzofurazan-4-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.21 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 38.22-8.00 (2H,m), 7.67-7.47 (1H, d, J=9.0 and 7.0 Hz), 7.47-7.10 (3H, m), 6.52 (1H, d,J=9.0 Hz), 5.94 (1H, d, J=18.0 Hz), 5.78 (1H, d, J=18.0 Hz), 4.70-4.49(1H, m), 4.60 (2H, s), 2.93 (1H, dd, J=17.8 and 4.2 Hz 2.35 (1H, dd,J=17.8 and 4.8 Hz), 1.35 (9H, s).

EXAMPLE 29(51)N-(3,5-dimethylisooxazol-4-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.64 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.35 (1H, d,J=9.0 Hz), 7.35 (1H, d, J=7.2 Hz), 7.19 (1H, dd, J=9.0 Hz, J=7.2 Hz),6.28 (1H, d, J=8.8 Hz), 5.85 and 5.68 (each 1H, d, J=18.0 Hz), 4.61 (2H,s), 4.16-4.00 (1H, m), 2.82 (1H, dd, J=17.4 Hz, J=4.4 Hz), 2.64 (3H, s),2.46 (1H, dd, J=17.4 Hz, J=4.6 Hz), 2.40 (3H, s), 1.40 (9H, s).

EXAMPLE 29(52)N-(2-benzyloxycarbonylaminoethyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.52 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.38-7.08 (8H,m), 6.10-5.93 (1H, m), 5.93-5.64 (2H, m), 5.48-5.25 (1H, m), 5.10 (2H,s), 4.60 (2H, s), 4.41-4.21 (1H, m), 3.80-3.55 and 3.55-3.18 (4H, m),3.03-2.62 (2H, m), 1.42 (9H, s).

EXAMPLE 29(53)N-(1,1-dioxotetrahydrothiophen-3-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.32 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.44-7.08 (3H,m), 6.12-5.87 (1H, m), 5.87-5.57 (2H, m), 4.62 (2H, s), 4.67-4.25 (1H,m), 4.25-3.80 (1H, m), 3.66-2.93 (4H, m), 2.93-2.30 (4H, m), 1.44 (9H,s).

EXAMPLE 29(54)N-(5-phenylcarbonylaminomethylthiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.38 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.86-7.70 (2H,m), 7.64-7.06 (7H, m), 7.02 (1H, d, J=3.8 Hz), 6.93-6.76 (1H, m), 6.15(1H, d, J=9.0 Hz), 5.78 (1H, d, J=18.0 Hz), 5.59 (1H, d, J=18.0 Hz),4.81 (2H, d, J=6.2 Hz), 4.58 (2H, s), 4.27-4.07 (1H, m), 2.90 (1H, dd,J=17.6 and 4.0 Hz), 2.47 (1H, dd, J=17.6 and 5.0 Hz), 1.38 (9H, s).

EXAMPLE 29(55)N-(2,1,3-benzothiadiazol-4-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.30 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.36-8.21 (2H,m), 7.75 (1H, dd, J=8.8 and 7.2 Hz), 7.42-7.11 (3H, m), 6.59 (1H, d,J=9.4 Hz), 5.90 (1H, d, J=18.0 Hz), 5.73 (1h, d, J=18.0 Hz), 4.72-4.47(1H, m), 4.59 (2H, s), 2.88 (1H, dd, J=17.6 and 3.6 Hz) 2.19 (1H, dd,J=17.6 and 4.8 Hz), 1.35 (9H, s).

EXAMPLE 29(56)N-(4-acetylaminophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.26 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.97 (1H, s),7.83 and 7.73 (each 2H, d, J=8.5 Hz), 7.34 (1H, d, J=9.0 Hz), 7.34 (1H,d, J=7.0 Hz), 7.20 (1H, dd, J=9.0 Hz, J=7.0 Hz), 6.10 (1H, d, J=9.2 Hz),5.77 and 5.65 (each 1H, d, J=19.0 Hz), 4.28 (2H, s), 4.23-4.04 (1H, m),2.96 (1H, dd, J=17.6 Hz, J=3.8 Hz), 2.46 (1H, dd, J=17.6 Hz, J=5.2 Hz),1.38 (9H, s).

EXAMPLE 29(57)N-(4-phenylthiophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.52 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.72 (2H, d,J=8.8 Hz), 7.59-7.13 (8H, m), 7.23 (2H, d, J=8.8 Hz), 6.20 (1H, d, J=9.0Hz), 5.88 and 5.66 (each 1H, d, J=18.8 Hz), 4.28 (2H, s), 4.19-4.05 (1H,m), 2.93 (1H, dd, J=17.6 Hz, J=3.8 Hz), 2.44 (1H, dd, J=17.6 Hz, J=4.6Hz), 1.36 (9H, s).

EXAMPLE 29(58)N-(2-nitrophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.61 (chloroform:methanol=19:1); NMR (CDCl₃): δ 8.20-8.06 and8.05-7.70 (4H, m), 7.34 (1H, d, J=9.0 Hz), 7.34 (1H, d, J=7.0 Hz), 7.18(1H, dd, J=9.0 Hz, J=7.0 Hz), 6.74 (1H, d, J=9.2 Hz,), 5.93 and 5.75(each 1H, d, J=18.0 Hz), 4.61 (2H, s), 4.42-4.25 (1H, m), 2.95 (1H, dd,J=17.6 Hz, J=4.2 Hz), 2.40 (1H, dd, J=17.6 Hz, J=4.4 Hz), 1.38 (9H, s).

EXAMPLE 29(59)N-(camphor-10-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.63 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.35 (1H, d,J=9.0 Hz), 7.35 (1H, d, J=6.8 Hz), 7.18 (1H, dd, J=9.0 Hz, J=6.8 Hz),6.61 (1H, d, J=8.0 Hz), 6.01 and 5.85 (each 1H, d, J=18.5 Hz), 4.64-4.33(1H, m), 4.61 (2H, s), 3.56-3.40 and 3.15-2.70 (4H, m 2.53-2.27 and2.27-1.82 (7H, m), 1.43 (9H, s), 1.02 (3H, s), 0.94 (3H, s).

EXAMPLE 29(60)N-(6-chloroimizazo[2,1-B]thiazol-5-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.19 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 7.93 (1H, d,J=4.4 Hz), 7.44-7.07 (4H, m), 6.76-6.53 (1H, m), 5.94 (1H, d, J=18.0Hz), 5.78 (1H, d, J=18.0 Hz), 4.61 (2H, s), 4.36-4.09 (1H, m), 2.91 (1H,dd, J=17.6 and 4.0 Hz), 2.48 (1H, dd, J=117.6 and 4.6 Hz), 1.39 (9H, s).

EXAMPLE 29(61)N-(5-(2-methylthiopyrimidin-4-yl)thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.19 (hexane:ethyl:acetate=2:1); NMR (CDCl₃): δ 8.58 (1H, d,J=5.2 Hz), 7.72-7.58 (2H, m), 7.41-7.10 (4H, m), 6.32 (1H, d, J=8.8 Hz),5.89 (1H, d, J=18.2 Hz), 5.70 (1H, d, J=18.2 Hz), 4.60 (2H, s),4.35-4.15 (1H, m), 2.92 (1H, dd, J=17.6 and 3.6 Hz), 2.61 (3H, s), 2.41(1H, dd, J=17.6 and 4.8 Hz), 1.38 (9H, s).

EXAMPLE 29(62)N-(4-butylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.67 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.77 (2H, d,J=8.8 Hz), 7.35 (2H, d, J=8.8 Hz), 7.40-7.12 (3H, m), 6.02 (1H, d, J=9.6Hz), 5.84 and 5.62 (each 1H, d, J=18.0 Hz), 4.59 (2H, s), 4.18-4.05 (1H,m), 2.82 (1H, dd, J=7.6 Hz, J=3.6 Hz), 2.70 (2H, t, J=7.5 Hz), 2.32 (1H,dd, J=17.6 Hz, J=5.0 Hz), 1.72-1.18 (4H, m), 1.37 (9H, s), 0.93 (3

EXAMPLE 29(63)N-(4-butylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.57 (chloroform:methanol=19:1); NMR (CDCl₃): δ 7.81 (2H, d,J=8.5 Hz), 7.45-7.15 (3H, m), 7.38 (2H, d, J=8.5 Hz), 5.98 (1H, d, J=9.0Hz), 5.76 and 5.63 (each 1H, d, J=18.6 Hz), 4.28 (2H, s), 4.20-4.03 (1H,m), 2.95 (1H, dd, J=17.6 Hz, J=3.6 Hz), 2.71 (2H, t, J=7.6 Hz), 2.36(1H, dd, J=17.6 Hz, J=5.0 Hz), 1.74-1.18 (4H, m), 1.37 (9H, s), 0.93(3H, s).

EXAMPLE 29(64)N-(5-(isooxazol-3-yl)thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.21 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.33 (1H, d,J=2.0 Hz), 7.63 (1H, d, J=3.8 Hz), 7.47 (1H, d, J=3.8 Hz), 7.40-7.11(3H, m), 6.56 (1H, d, J=2.0 Hz), 6.37 (1H, d, J=8.0 Hz), 5.88 (1H, d,J=17.8 Hz), 5.69 (1H, d, J=17.8 Hz), 4.60 (2H, s), 4.34-4.12 (1H, m),2.90 (1H, dd, J=17.2 and 3.8 Hz), 2.44 (1H, dd, J=17.2 and 4.8 Hz), 1.38(9H, s).

EXAMPLE 29(65)N-(5-(4-chlorophenylcarbonylaminomethyl)thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.31 (hexane:ethyl:acetate=1:1); NMR (CDCl₃): δ 7.82-7.65 (2H,m), 7.55-6.90 (8H, m), 6.18 (1H, d, J=9.0 Hz), 5.75 (1H, d, J=17.8 Hz),5.56 (1H, d, J=17.8 Hz), 4.78 (2H, d, J=6.0 Hz), 4.57 (2H, s), 4.28-4.10(1H, m), 2.90 (1H, dd, J=17.4 and 4.0 Hz), 2.51 (1H, dd, J=17.4 and 5.0Hz), 1.38 (9H, s).

EXAMPLE 29(66)N-(4-(pyrrolidin-1-yl)phenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.43 (hexane:ethyl acetate=1:1); NMR (DMSO-d₆): δ 8.27-8.06 (1H,brs), 7.80-7.19 (5H, m), 6.71-6.46 (2H, m), 6.04-5.70 (2H, m), 4.44-3.90(3H, m), 3.35-3.05 (4H, m), 2.74-2.49 (2H, m), 2.03-1.76 (4H, m), 1.34(9H, s).

EXAMPLE 29(67)N-(4-(morpholin-4-yl)phenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.19 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.85-7.66 (2H,m), 7.47-7.10 (3H, m), 7.02-6.85 (2H, m), 5.83 (1H, d, J=9.4 Hz), 5.73(1H, d, J=18.8 Hz), 5.61 (1H, d, J=18.8 Hz), 4.25 (2H, s), 4.15-4.00(1H, m), 3.94-3.76 (4H, m), 3.40-3.22 (4H, m), 2.98 (1H, dd, J=17.6 and4.2 Hz), 2.47 (1H, dd, J=17.6 and 4.6 Hz), 1.39 (9H, s).

EXAMPLE 29(68)N-(2-diethylaminoethyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.67 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.34 (1H, d, J=8.8Hz), 7.34 (1H, d, J=7.0 Hz), 7.17 (1H, dd, J=8.8 Hz, 7.0 Hz), 5.87 and5.78 (each 1H, d, J=18.0 Hz), 4.61 (2H, s), 4.53-4.43 (1H, m), 3.47-2.41(10H, m), 1.42 (9H, s), 1.05 (3H, t, J=7.0 Hz).

EXAMPLE 29(69)N-(3-methylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.23 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.74-7.59 (2H,m), 7.51-7.10 (5H, m), 6.06 (1H, d, J=9.6 Hz), 5.83 (1H, d, J=18.2 Hz),5.62 (1H, d, J=18.2 Hz), 4.59 (2H, s), 4.21-4.05 (1H, m), 2.82 (1H, dd,J=17.4 and 3.8 Hz), 2.44 (3H, s), 2.24 (1H, dd, J=17.4 and 5.0 Hz), 1.37(9H, s).

EXAMPLE 29(70)N-(4-isopropylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.31 (hexane:ethyl acetate=3:1); NMR (CDCl₃): δ 7.86-7.71 (2H,m), 7.46-7.10 (5H, m), 6.04 (1H, d, J=9.6 Hz), 5.84 (1H, d, J=18.0 Hz),5.61 (1H, d, J=18.0 Hz), 4.59 (2H, s), 4.20-4.01 (1H, m, 3.10-2.87 (1H,m), 2.83 (1H, dd, J=17.6 and 3.6 Hz), 2.27 (1H, dd, J=17.6 and 5.0 Hz),1.36 (9H, s), 1.27 (6H, d, J=7.0 Hz).

EXAMPLE 29(71)N-(4-isopropylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.26 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.90-7.73 (2H,m), 7.51-7.15 (5H, m), 5.98 (1H, d, J=9.6 Hz), 5.76 (1H, d, J=18.8 Hz),5.63 (1H, d, J=18.8 Hz), 4.29 (2H, s), 4.22-4.02 (1H, m), 3.13-2.83 (2H,m), 2.39 (1H, dd, J=17.8 and 4.4 Hz), 1.37 (9H, s), 1.29 (6H, d, J=6.8Hz).

EXAMPLE 29(72)N-(2-diethylaminoethyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.37 (chloroform:methanol=9:1); NMR (CDCl₃): δ 7.43-7.15 (3H, m),5.81 (2H, s), 4.60-4.47 (1H, m), 4.39-4.26 (2H, m), 3.41-2.45 (10H, m),1.42 (9H, s), 1.08 (3H, t, J=7.0 Hz).

EXAMPLE 29(73)N-(4-butyloxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

TLC:Rf 0.51 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.92-7.69 (2H,m), 7.28-7.10 (3H, m), 7.10-6.89 (2H, m), 6.00 (1H, d, J=8.6 Hz), 5.86(1H, d, J=18.2 Hz), 5.65 (1H, d, J=18.2 Hz), 4.60 (2H, s), 4.22-3.89(3H, m), 2.83 (1H, dd, J=17.2 and, 3.4 Hz), 2.27 (1H, dd, J=17.2 and 4.8Hz), 1.94-1.69 (2H, m), 1.64-1.24 (2H, m), 1.37 (9H, s), 0.99 (3H, t,J=7.4 Hz).

EXAMPLE 29(74)N-(4-butyloxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

TLC:Rf 0.28 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 7.91-7.74 (2H,m), 7.46-7.14 (3H, m), 7.10-6.93 (2H, m), 6.03-5.82 (1H, brs), 5.76 (1H,d, J=19.2 Hz), 5.64 (1H, d, J=19.2 Hz), 4.27 (2H, s), 4.18-3.97 (1H, m),4.04 (2H, t, J=6.4 Hz), 2.96 (1H, dd, J=17.4 and 4.0 Hz), 2.39 (1H, dd,J=17.4 and 4.6 Hz), 1.92-1.67 (2H, m), 1.67-1.35 (2H, m), 1.38 (9H, s),0.99 (3H, t, J=7.4 Hz).

EXAMPLE 30(1)-30(74)

By the same procedure as provided in example 6(-1), and if necessary,the compound prepared in example 29(1)-29(74), the compounds of thecompound prepared in example 29(1)-29(74), the compounds of the

EXAMPLE 30(1)N-(4-t-butylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.19 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ8.83-8.34 (1H, br), 7.92-7.75 (2H, m), 7.72-7.31 (5H, m), 6.10-5.54 (2H,br), 4.43-4.26 (1H, m), 4.30 (2H, s), 2.82-2.50 (2H, m), 1.30 (9H, s).

EXAMPLE 30(2)N-phenylmethylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.14 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ7.99-7.70 (1H, br), 7.52 (2H, d, J=7.5 Hz), 7.45-7.27 (6H, m), 6.01-5.80(2H, m), 4.52 (total 4H, s), 4.58-4.38 (1H, m), 2.77-2.66 (2H, m).

EXAMPLE 30(3)N-phenylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=18:1:1);NMR(CDCl₃+DMSO-d₆): δ 7.98-7.80 and 7.68-7.10 (total 9H, m), 6.10-5.30(2H, br), 4.58 (2H, s), 4.30-4.10 (1H, m), 2.76-2.33 (2H, m).

EXAMPLE 30(4)N-(2-(naphthalen-1-yl)ethyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.59 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.10-7.75 and 7.65-7.13 (total 11H, m), 6.10-5.87 (2H, m), 4.89 (2H, s),4.55-4.38 (1H, m), 3.60-3.46 (4H, m), 2.75-2.62 (2H, m).

EXAMPLE 30(5)N-(naphthalen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.80-12.10 (1H, br), 8.72-8.47 (2H, m), 8.23-8.00 (3H, m), 7.94-7.83(1H, m), 7.79-7.60 (2H, m), 7.57-7.45 (2H, m), 7.43-7.29 (1H, m),6.15-5.77 (2H, m), 4.49 (2H, s), 4.43-4.29 (1H, m), 2.64-2.37 (2H, m).

EXAMPLE 30(6)N-(naphthalen-1-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.54 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.70-12.20 (1H, br), 8.99-8.75 (1H, m), 8.70-8.57 (1H, m), 8.32-8.15and 8.15-8.02 (total 3H, m), 7.78-7.56 (3H, m), 7.56-7.46 (2H, m),7.42-7.30 (1H, m), 6.00-5.70 (2H, m), 4.49 (2H, s), 4.42-4.25 (1H, m),2.42-2.21 (2H, m).

EXAMPLE 30(7)N-(2-phenylethenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.57 (chloroform:methanol:acetic acid=25:1:1); NMR (DMSO-d₆): δ8.90-8.40 (1H, br), 7.72-7.68 (2H, m), 7.55-7.15 (8H, m), 6.10-5.90 (2H,m), 4.51 (2H, s), 4.45-4.35 (1H, m), 2.80-2.72 (2H, m).

EXAMPLE 30(8)N-(4-bromophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.50 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.85-8.25 (1H, br), 7.86-7.70 (4H, m), 7.56-7.30 (3H, m), 6.07-5.72 (2H,m), 4.51 (2H, s), 4.43-4.27 (1H, m), 2.69-2.52 (2H, m).

EXAMPLE 30(9)N-butylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.30 (chloroform:methanol:acetic acid=25:1:1); NMR (DMSO-d₆): δ7.94-7.72 (1H, d), 7.53-7.33 (3H, m), 6.16-5.85 (2H, m), 4.52 (2H, s),4.50-4.40 (1H, m), 3.18-3.10 (2H, m), 2.77-2.73 (2H, m), 1.75-1.55 (2H,m), 1.48-1.28 (2H, m), 0.90 (3H, t).

EXAMPLE 30(10)N-(quinolin-8-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.42 (chloroform:methanol:acetic acid=25:1:1); NMR (DMSO-d₆): δ9.05-9.01 (1H, m), 8.58-8.53 (1H, m), 8.39-8.29 (2H, m), 8.17-8.00 (1H,m), 7.80-7.67 (2H, m), 7.53-7.33 (3H, m), 6.16-5.63 (2H, m), 4.91-4.73(1H, m), 4.49 (2H, s).

EXAMPLE 30(11)N-(5-dimethylaminonaphthalen-1-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=30:1:1); NMR (DMSO-d₆): δ12.84-11.80 (1H, br), 8.94-8.64 (1H, m), 8.52-8.47 (1H, m), 8.30-8.19(2H, m), 7.66-7.23 (6H, m), 5.93-5.68 (2H, m), 4.49 (2H, s), 4.42-4.26(1H, m), 2.83 (6H, s), 2.60-2.25 (2H, m).

EXAMPLE 30(12)N-(4-nitrophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.53 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.40 (2H, d, J=9.0 Hz), 8.10 (2H, d, J=9.0 Hz), 7.51 (1H, d, J=9.0 Hz),7.50 (1H, d, J=6.8 Hz), 6.10-5.75 (2H, br), 4.50 (2H, s), 4.55-4.37 (1H,m), 2.68-2.55 (2H, m).

EXAMPLE 30(13)N-phenylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ13.04-12.28 (1H, br), 8.68-8.50 (1H, m), 7.94-7.89 (2H, m), 7.68-7.34(6H, m), 6.04-5.79 (2H, m), 4.46-4.36 (1H, m), 4.29 (2H, m), 2.79-2.56(2H, m).

EXAMPLE 30(14)N-(2-fluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.36 (chloroform:methanol:acetic acid=25:1:1); NMR (DMSO-d₆): δ12.94-12.36 (1H, br), 8.86-8.70 (1H, m), 7.88-7.33 (7H, m), 5.97 (2H,brs), 4.52 (2H, s), 4.46 (1H, m), 2.78-2.47 (2H, m).

EXAMPLE 30(15)N-(4-fluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol:acetic acid=25:1:1); NMR (DMSO-d₆): δ13.09-12.00 (1H, br), 8.62-8.46 (1H, m), 7.96-7.89 (2H, m), 7.53-7.32(5H, m), 6.07-5.83 (2H, m), 4.51 (2H, s), 4.35 (1H, m), 2.56 (2H, m).

EXAMPLE 30(16)N-(3-fluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.17 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ8.60 (1H, br), 7.75-7.32 (7H, m), 6.20-5.70 (2H, m), 4.51 (2H, s),4.46-4.32 (1H, m), 2.62-2.53 (2H, m).

EXAMPLE 30(17)N-(2-bromophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.27 (chloroform:methanol:acetic acid=8:1:1); NMR (DMSO-d₆): δ12.80-12.20 (1H, brs), 8.80-8.40 (1H, m), 8.12-8.00 and 7.90-7.79 (each1H, m), 7.65-7.46 and 7.46-7.32 (total 5H, m), 6.15-6.15-5.75 (2H, m),4.51 (2H, s), 4.60-4.30 (1H, m), 2.80-2.42 (2H, m).

EXAMPLE 30(18)N-(4-methoxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=25:1:1); NMR (DMSO-d₆): δ8.48-8.16 (1H, m), 7.82-7.78 (2H, m), 7.53-7.08 (5H, m), 6.15-5.63 (2H,m), 4.51 (2H, s), 4.33-4.15 (1H, m), 3.85 (3H, s).

EXAMPLE 30(19)N-(4-trifluoromethylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.35 (chloroform:methanol:acetic acid=25:1:1); NMR (DMSO-d₆): δ8.07 (2H, d, J=8.5 Hz), 7.96 (2H, t, J=8.5 Hz), 7.53-7.33 (3H, m),6.08 5.65 (2H, m), 4.51 (2H, s), 4.46-4.55 (1H, m), 2.61-2.58 (2H, m).

EXAMPLE 30(20)N-(thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.38 (chloroform:methanol:acetic acid=25:1:1); NMR (DMSO-d₆): δ13.13-11.94 (1H, br), 8.92-8.46 (1H, m), 7.95 (1H, dd, J=5.0, 1.4 Hz),7.70 (1H, m), 7.53-7.49 (2H, m,), 7.40-7.32 (1H, m), 7.18 (1, dd, J=5.0,4.0 Hz), 6.08-5.78 (2H, m), 4.52 (2H, s), 4.39 (1H, m), 2.57 (2H, m).

EXAMPLE 30(21)N-(3-phenylpropyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.57 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.00-7.80 (1H, m), 7.56-7.47 and 7.43-7.13 (8H, m), 6.12-5.82 (2H, m),4.52 (2H, s), 4.56-4.40 (1H, m), 3.22-3.07 (2H, m), 2.80-2.60 (4H, m),2.06-1.87 (2H, m).

EXAMPLE 30(22)N-(2-fluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.35 (chloroform:ethanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.9 (1H, br), 7.95-7.30 (7H, m), 5.94 (2H, br), 4.54 (1H, m), 4.30 (2H,brs), 2.74 (2H, m).

EXAMPLE 30(23)N-(4-chlorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.15 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ13.00-12.20 (1H, br), 8.78-8.40 (1H, br), 7.87 and 7.65 (each 2H, d,J=8.6 Hz), 7.52 (1H, d, J=8.6 Hz), 7.51 (1H, d, J=7.4 Hz), 7.41 (1H, dd,J=8.6 Hz, 7.4 Hz), 6.15-5.76 (2H, br), 4.51 (2H, s), 4.45-4.27 (1H, m),2.67-2.53 (2H, m).

EXAMPLE 30(24)N-(3-chlorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.15 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ12.80-12.40 (1H, brs), 8.64 (1H, d, J=7.4 Hz), 7.90-7.70 and 7.42-7.32(7H, m), 6.02 and 5.89 (each 1H, d, J=18.4 Hz), 4.51 (2H, s), 4.57-4.38(1H, m), 2.66-2.55 (2H, m).

EXAMPLE 30(25)N-(2-chlorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.21 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ12.80-11.80 (1H, brs), 8.80-8.50 (1H, m), 8.02 (1H, d, J=7.4 Hz),7.73-7.45 and 7.45-7.30 (6H, m), 6.10-5.80 (2H, m), 4.51 (2H, s),4.57-4.32 (1H, m), 2.77-2.40 (2H, m).

EXAMPLE 30(26)N-(2-phenyloxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.26 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ12.80-12.20 (1H, brs), 8.39-8.27 (1H, m), 7.95-7.85 (1H, m), 7.65-7.05and 6.99-6.82 (11H, m), 6.03 and 5.91 (each 1H, d, J=18.4 Hz), 4.52 (2H,s), 4.60-4.40 (1H, m), 2.80-2.47 (2H, m).

EXAMPLE 30(27)N-(2-phenylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.38 (chloroform:methanol:water=50:10:1); NMR (DMSO-d₆): δ 8.05(1H, dd, J=1.0, 7.6 Hz), 7.68-7.30 (12H, m), 5.79 (2H, brs), 4.49 (2H,s), 3.96 (1H, m), 2.48-2.28 (2H, m).

EXAMPLE 30(28)N-(3-phenylpropyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.43 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.10-12.20 (1H, brs), 8.10-7.90 (1H, m), 7.61-7.13 (8H, m), 6.13-5.75(2H, br), 4.65-4.47 (1H, m), 4.35 (2H, s), 3.25-3.10 (2H, m), 2.91-2.79(2H, m) 2.79-2.64 (2H, m), 2.11-1.87 (2H, m).

EXAMPLE 30(29)N-(2-methoxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.51 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.90-12.10 (1H, brs), 8.10-7.90 (1H, m), 7.80-7.01 (7H, m), 6.10-5.70(2H, br), 4.50 (2H, s), 4.53-4.33 (1H, m), 3.85 (3H, s), 2.67-2.39 (2H,m).

EXAMPLE 30(30)N-(2,6-difluorophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.48 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.80-7.60, 7.60-7.47 and 7.47-7.17 (6H, m), 6.10-5.80 (2H, br),4.63-4.52 (1H, m), 4.51 (2H, m), 2.85-2.43 (2H, m).

EXAMPLE 30(31)N-(4-cyanophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.08 (2H, d, J=8.6 Hz), 8.00 (2H, d, J=8.6 Hz), 7.52 (1H, d, J=9.0 Hz),7.51 (1H, d, J=6.8 Hz), 7.37 (1H, dd, J=9.0 Hz, 6.8 Hz), 6.10-5.75 (2H,br), 4.51 (2H, s), 4.48 (1H, m), 2.68-2.55 (2H, m).

EXAMPLE 30(32)N-(2-methylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.50 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.95-8.20 (1H, br), 7.90 (1H, d, J=7.6 Hz), 7.70-7.08 (6H, m), 6.30-5.42(2H, br), 4.52 (2H, s), 4.30 (1H, brs), 2.58 (3H, s), 2.84-2.12 (2H, m).

EXAMPLE 30(33)N-(4-methylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.44 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.79-8.03 (1H, br), 7.76 (2H, d, J=8.0 Hz), 7.61-7.20 (5H, m), 6.32-5.42(2H, br), 4.51 (2H, s), 4.43-4.14 (1H, m), 2.71-2.12 (2H, m), 2.39 (3H,s).

EXAMPLE 30(34)N-(4-phenylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.25 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ13.45-11.25 (1H, br), 8.87-8.27 (1H, br), 8.13-7.80 (4H, m), 7.76 (2H,d, J=6.6 Hz), 7.65-7.23 (6H, m), 6.33-5.55 (2H, br), 4.51 (2H, s),4.58-4.20 (1H, m), 2.82-2.35 (2H, m).

EXAMPLE 30(35)N-(5-dibutylaminonaphthalen-1-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.33 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ13.20-11.60 (1H, br), 9.10-8.49 (1H, br), 8.57 (1H, d, J=8.4 Hz), 8.33(1H, d, J=8.2 Hz), 8.20 (1H, d, J=7.0 Hz), 7.75-7.22 (6H, m), 6.09-5.18(2H, br), 4.47 (2H, s), 4.46-4.18 (1H, m), 3.08 (4H, t, J=7.4 Hz),2.68-2.20 (2H, m), 1.54-0.97 (8H, m), 0.76 (6H, t, J=6.8 Hz).

EXAMPLE 30(36)N-(3-phenylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.65 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.00-12.10 (1H, br), 8.71-8.40 (1H, br), 8.17-8.10, 8.00-7.79,7.79-7.60 and 7.60-7.30 (12H, m), 6.15-5.73 (2H, br), 4.49 (2H, s),4.55-4.35 (1H, m), 2.64-2.40 (2H, m).

EXAMPLE 30(37)N-(4-acetylaminophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.32 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.90-12.10 (1H, br), 10.34 (1H, s), 8.43-8.25 (1H, br), 7.83-7.70 (4H,m), 7.53 (1H, d, J=9.0 Hz), 7.52 (1H, d, J=6.8 Hz), 7.37 (1H, dd, J=9.0Hz, 6.8 Hz), 6.10-5.77 (2H, br), 4.51 (2H, s), 4.39-4.20 (1H, m),2.62-2.37 (2H, m) 2.09 (3H, s).

EXAMPLE 30(38)N-(4-t-butylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol:acetic acid=35:1:1); NMR (DMSO-d₆): δ13.15-11.35 (1H, br), 8.86-8.03 (1H, br), 7.79 (2H, d, J=8.6 Hz), 7.61(2H, d, J=8.6 Hz), 7.56-7.26 (3H, m), 6.24-5.42 (2H, br), 4.50 (2H, s),4.40-4.20 (1H, m), 2.63-2.37 (2H, m), 1.29 (9H, s).

EXAMPLE 30(39)N-(5-dimethylaminonaphthalen-1-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.12 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ9.46-8.63 (11H, br), 8.49 (1H, d, J=8.4 Hz), 8.40-8.16 (2H, m),7.74-7.15 (6H, m), 5.70 (2H, br), 4.48-4.32 (1H, m), 4.16 (2H, s), 2.81(6H, s), 2.70-2.40 (2H, m).

EXAMPLE 30(40)N-(5-(pyridin-2-yl)thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.22 (chloroform:methanol:acetic acid=35:1:1); NMR (DMSO-d₆): δ8.84 (1H, d, J=7.8 Hz), 8.59 (1H, d, J=4.4 Hz), 8.06 (1H, d, J=7.8 Hz),8.00-7.80 (2H, m), 7.71 (2H, d, J=4.2 Hz), 7.58-7.27 (4H, m), 6.05 (2H,d, J=18.1 Hz), 5.91s(1Hd, J=128.1 Hz), 4.61-4.30 (1H, m), 4.49 (2H, s),2.77-2.46 (2H, m).

EXAMPLE 30(41) N-(1-(3-chloro-5-trifluoromethylpyridin-2-yl)pyrrol-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.16 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ13.50-11.80 (1H, br), 8.95 (1H, brs), 8.77 (1H, brs), 8.41-8.17 (1H, m),8.00 (1H, brs), 7.64-7.00 (4H, m), 6.66 (1H, brs), 6.23-5.68 (2H, m),4.55-4.14 (1H, m), 4.50 (2H, s), 2.75-2.28 (2H, m).

EXAMPLE 30(42)N-(4-phenyloxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ8.60-8.25 (1H, br), 7.93-7.79 (2H, m), 7.60-7.05 (10H, m), 6.10-5.70(2H, br), 4.51 (2H, s), 4.40-4.23 (1H, m), 2.65-2.35 (2H, m).

EXAMPLE 30(43)N-(4-phenylthiophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ8.67-8.25 (1H, br), 7.83-7.72 (2H, m), 7.60-7.25 (10H, m), 6.12-5.65(2H, br), 4.51 (2H, s), 4.40-4.23 (1H, m), 2.65-2.33 (2H, m).

EXAMPLE 30(44)N-octanylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid

TLC:Rf 0.17 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ8.00-7.64 (1H, br), 7.60-7.30 (3H, m), 6.20-5.63 (2H, br), 4.61-4.33(1H, m), 4.52 (2H, s), 3.25-3.00 (2H, m), 2.88-2.60 (2H, m), 1.82-1.48(2H, m), 1.48-1.06 (10H, m), 0.97-0.70 (3H, m).

EXAMPLE 30(45)N-(4-phenylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.10 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ9.23-8.40 (1H, br), 8.06-7.82 (4H, m), 7.82-7.64 (2H, m), 7.64-7.24 (6H,m), 6.26-5.45 (2H, br), 4.56-4.30 (1H, m), 4.33 (1H, d, J=18.0 Hz), 4.22(1H, d, J=18.0 Hz), 2.90-2.50 (2H, m).

EXAMPLE 30(46)N-(4-phenylcarbonylmethylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.61 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d): δ8.70-8 .20 (1H, br), 8.10-7.99 ,7.88-7 .78 and 7.78-7.33 (total 12H, m),6.10-5.64 (2H, br), 4.56 (2H, s), 4.51 (2H, s), 4.40-4.27 (1H, m),2.60-2.38 (2H, m).

EXAMPLE 30(47)N-(2-acetylamino-4-methylthiazol-5-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.35 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.70-12.35 (1H, br), 7.52 (1H, d, J=9.0 Hz), 7.52 (1H, d, J=7.0 Hz),7.37 (1H, dd, J=9.0 Hz, 7.0 Hz), 6.12-5.71 (2H, br), 4.51 (2H, s),4.39-4.23 (1H, m), 2.64-2.38 (2H, m) 2.50 (3H, s), 2.17 (3H, s).

EXAMPLE 30(48)N-(2,2,2-trifluoroethylsulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.32 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.52 (1H, d, J=9.4 Hz), 7.52 (1H, d, J=6.8 Hz), 7.37 (1H, dd, J=9.4 Hz,6.8 Hz), 6.20-5.80 (2H, br), 4.72-4.45 (3H, m), 4.52 (2H, s), 2.89-2.65(2H, m).

EXAMPLE 30(49)N-(2-trifluoromethylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=35:1:1); NMR (DMSO-d₆): δ13.10-11.85 (1H, br), 9.22-8.18 (1H, br), 8.26-8.12 (1H, m), 8.22-7.76(2H, m), 7.52 (1H, d,.J=9.0 Hz), 7.52 (1H, d, J=7.0 Hz), 7.37 (1H, dd,J=9.0 and 7.0 Hz), 6.25-5.60 (2H, br), 4.63-4.34 (1H, m), 4.51 (2H, s),2.83-2.49 (2H, m).

EXAMPLE 30(50)N-(benzofurazan-4-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.18 (chloroform:methanol:acetic acid=35:1:1); NMR (DMSO-d₆): δ12.80-11.80 (1H, br), 9.50-8.82 (1H, br), 8.36 (1H, d, J=9.0 Hz), 8.12(1H, d, J=6.8 Hz), 7.74 (1H, dd, J=9.0 and 6.8 Hz), 7.52 (1H, d, J=9.1Hz), 7.52 (1H, d, J=7.1 Hz), 7.37 (1H, dd, J=9.1 and 7.1 Hz), 5.98 (2H,s), 4.75-4.41 (1H, m), 4.50 (2H, s), 2.85-2.42 (2H, m).

EXAMPLE 30(51)N-(3,5-dimethylisooxazol-4-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.50 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.10-11.90(1H, br), 9.20-8.40 (1H, br), 7.52 (1H, d, J=8.8 Hz), 7.52(1H, d, J=7.0 Hz), 7.37 (1H, dd, J=8.8 Hz, 7.0 Hz), 6.15-5.80 (2H, br),4.52 (2H, s), 4.42-4.30 (1H, m), 2.82-2.35 (2H, m), 2.57 (3H, s), 2.32(3H, s).

EXAMPLE 30(52)N-(2-benzyloxycarbonylaminoethyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.42 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.10-7.65 (1H, br), 7.58-7.20 (8H, m), 6.15-5.80 (2H, br), 5.01 (2H, s),4.57-4.40 (1H, m), 4.52 (2H, s), 3.80-2.90 (4H, m), 2.90-2.60 (2H, m).

EXAMPLE 30(53)N-(1,1-dioxotetrahydrothiophen-3-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.14 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ7.64-7.22 (3H, m), 5.97 (2H, brs), 4.68-4.14 (2H, m), 4.52 (2H, s),3.85-3.00 (4H, m),-2.90-2.20 (4H, m).

EXAMPLE 30(54)N-(5-phenylcarbonylaminomethylthiophen-2-yl)'sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.16 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ9.30 (1H, t, J=5.8 Hz), 7.88 (2H, d, J=6.6 Hz), 7.66-6.99 (8H, m), 6.06-5.70 (2H, m), 4.66 (2H, d, J=5.8 Hz), 4.50 (2H, s), 4.17 (1H, t, J=6.2Hz), 2.64-2.23 (2H, m).

EXAMPLE 30(55)N-(2,1,3-benzothiadiazol-4-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=40:1:1); NMR (DMSO-d₆): δ13.30-11.70 (1H, br), 9.20-8.00 (1H, br), 8.38 (1H, d, J=9.0 Hz), 8.25(1H, d, J=6.0 Hz), 7.85 (i H, dd, J=9.0 and 6.0 Hz), 7.52 (2H, m), 7.38(1H, dd, J=9.0 and 6.8 Hz), 6.25-5.52 (2H, m), 5.00-4.64 (1H, m), 4.49(2H, s), 2.89-2.35 (2H, m).

EXAMPLE 30(56)N-(4-acetylaminophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.39 (chloroform:methanol:acetic acid=8:1:1); NMR (DMSO-d₆): δ10.39 (1H, s), 7.88-7.70 (4H, m), 7.56-7.34 (3H, m), 6.03-5.70 (2H, br),4.33 and 4.22 (each 1H, d, J=15.0 Hz), 4.12-4.00 (1H, m), 2.55-2.22 (2H,m), 2.07 (3H, s).

EXAMPLE 30(57)N-(4-phenylthiophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.47 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.00-11.90 (1H, br), 9.00-8.40 (1H, br), 7.81 (2H, d, J=8.2 Hz),7.60-7.38 (8H, m), 7.32 (2H, d, J=8.2 Hz), 6.02-5.65 (2H, br), 4.45-4.31(1H, m), 4.29 (2H, s), 2.81-2.52 (2H, m).

EXAMPLE 30(58)N-(2-nitrophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.52 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.90-12.00 (1H, br), 9.20-8.35 (1H, br), 8.15-7.80 (4H, m), 7.52 (1H,d, J=9.0 Hz), 7.52 (1H, d, J=7.0 Hz), 7.37 (1H, dd, J=9.0 Hz, J=7.0 Hz),6.10-5.70 (2H, br), 4.65-4.45 (1H, m), 4.51 (2H, s), 2.85-2.55 (2H, m).

EXAMPLE 30(59)N-(camphor-10-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.57 and 0.49 (chloroform:methanol:acetic acid=18:1:1); NMR(DMSO-d₆): δ 13.10-11.90 (1H, br), 8.00-7.74 (1H, br), 7.52 (1H, d,J=9.0 Hz), 7.52 (1H, d, J=6.8 Hz), 7.37 (1H, dd, J=9.0 Hz, J=6.8 Hz),6.18-5.79 (2H, br), 4.65-4.45 (1H, m), 4.52 (2H, s), 3.54, 3.45, 3.20and 3.13 (total 2H, each d, J=14.0 Hz), 2.87-2.68 (2H, m), 2.46-2.36,2.10-1.81 and 1.62-1.30 (total 7H, m), 1.03 (3H, s), 0.82 and 0.81(total 3H, each s).

EXAMPLE 30(60)N-(6-chloroimizazo[2,1-B]thiazol-5-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.40 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.01 (1H, d, J=4.6 Hz), 7.59 (1H, d, J=4.6 Hz), 7.56-7.25 (3H, m),6.12-5.74 (2H, br), 4.51 (2H, s), 4.40 (1H, t, J=6.0 Hz), 2.85-2.46 (2H,m).

EXAMPLE 30(61)N-(5-(2-methylthiopyrimidin-4-yl)thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.34 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.10-12.20 (1H, br), 9.44-8.40 (1H, br), 8.72 (1H, d, J=5.2 Hz), 8.10(1H, d, J=4.1 Hz), 7.81 (1H, d, J=5.2 Hz), 7.76 (1H, d, J=4.1 Hz),7.60-7.23 (3H, m), 6.25-5.70 (2H, br), 4.49 (3H, brs), 2.96-2.33 (2H,m), 2.57 (3H, s).

EXAMPLE 30(62)N-(4-butylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.35 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ13.10-11.90 (1H, br), 8.55-8.20 (1H, br), 7.77 (2H, d, J=8.0 Hz), 7.52(1H, d, J=9.0 Hz), 7.52 (1H, d, J=7.2 Hz), 7.41 (2H, d, J=8.0 Hz), 7.37(1H, dd, J=9.0 Hz, J=7.2 Hz), 6.10-5.58 (2H, br), 4.51 (2H, s),4.39-4.20 (1H, m), 2.66 (2H, t, J=7.6 Hz), 2.56-2.32 (2H, m), 1.66-1.45and 1.37-1.14 (each 2H, m), 0.87 (3H, t, J=7.4 Hz).

EXAMPLE 30(63)N-(4-butylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.17 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ12.90-11.50 (1H, br), 8.80-8.10 (1H, br), 7.81 (2H, d, J=8.4 Hz),7.60-7.32 (3H, m), 7.42 (2H, d, J=8.4 Hz), 6.03-5.60 (2H, br), 4.42-4.12(3H, m), 2.80-2.58 (4H, m), 1.65-1.43 and 1.40-1.15 (each 2H, m), 0.87(3H, t, J=7.4 Hz).

EXAMPLE 30(64)N-(5-(isooxazol-3-yl)thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.38 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.73 (1H, d, J=1.8 Hz), 7.89-7.64 (2H, m), 7.64-7.23 (3H, m), 7.10 (1H,d, J=1.8 Hz), 6.27-5.55 (2H, br), 4.63-4.30 (3H, m), 2.92-2.47 (2H, m).

EXAMPLE 30(65)N-(5-(4-chlorophenylcarbonylaminomethyl)thiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.18 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₈): δ9.36 (1H, t, J=5.8 Hz), 8.03-7.76 (2H, m), 7.76-7.27 (5H, m), 7.09 (1H,d, J=4.0 Hz), 6.06-5.61 (2H, m), 4.66 (2H, d, J=5.8 Hz), 4.50 (2H, s),4.30 (1H, t, J=6.0 Hz), 2.69-2.37 (2H, m).

EXAMPLE 30(66)N-(4-(pyrrolidin-1-yl)phenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.49 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.33-7.94 (1H, br), 7.83-7.18 (5H, m), 6.74-6.45 (2H, m), 6.07-5.51 (2H,br), 4.39-4.00 (3H, m), 3.45-3.00 (4H, m), 2.92-2.58 (2H, m), 2.10-1.70(4H, m).

EXAMPLE 30(67)N-(4-(morpholin-4-yl)phenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.24 (chloroform:methanol:acetic acid=20:1:1); NMR (DMSO-d₆): δ8.62-7.90 (1H, br), 7.81-7.61 (2H, m), 7.61-7.17 (3H, m), 7.17-6.97 (2H,m), 6.02-5.57 (2H, m), 4.44-4.02 (3H, m), 3.95-3.5 (4H, m), 3.30-3.00(4H, m), 2.78-2.40 (2H, m).

EXAMPLE 30(68)N-(2-diethylaminoethyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.40 (chloroform:methanol:acetic acid=6:2:2); NMR (DMSO-d₆): δ8.50-8.10 (1H, br), 7.53 (2H, d, J=8.8 Hz), 7.52 (2H, d, J=7.4 Hz), 7.34(2H, d, J=8.8 Hz, 7.4 Hz), 6.06 (2H, br), 4.65-4.40 (1H, m), 4.52 (2H,s), 3.84-3.00 (8H, m), 3.00-2.83 (2H, m), 1.22 (6H, t, J=7.0 Hz).

EXAMPLE 30(69)N-(3-methylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.22 (chloroform:methanol:acetic acid=40:1:1); NMR (DMSO-d₆): δ13.45-11.42 (1H, br), 8.79-8.10 (1H, br), 7.83-7.10 (7H, m), 6.20-5.54(2H, br), 4.51 (2H, s), 4.43-4.20 (1H, m), 2.69-2.22 (2H, m), 2.39 (3H,s).

EXAMPLE 30(70)N-(4-isopropylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.31 (chloroform:methanol:acetic acid=40:1:1); NMR (DMSO-d₆): δ13.60-11.40 (1H, br), 8.82-8.03 (1H, br), 7.93-7.65 (2H, m), 7.65-7.10(5H, m), 6.28-5.39 (2H, br), 4.51 (2H, s), 4.43-4.17 (1H, m), 3.10-2.81(1H, m), 2.78-2.29 (2H, m), 1.21 (6H, d, J=6.8 Hz).

EXAMPLE 30(71)N-(4-isopropylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.41 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.40-11.70 (1H, br), 8.89-8.20 (1H, br), 7.95-7.69 (2H, m), 7.69-7.05(5H, m), 6.18-5.50 (2H, br), 4.52-4.14 (1H, m), 4.30 (2H, s), 3.07-2.85(1H, m), 2.85-2.43 (2H, m), 1.21 (6H, d, J=6.8 Hz).

EXAMPLE 30(72)N-(2-diethylaminoethyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.hydrochloric acid salt

TLC:Rf 0.32 (chloroform:methanol:acetic acid=6:2:2); NMR (DMSO-d₆): δ7.55 (1H, d, J=9.2 Hz), 7.55 (1H, d, J=6.8 Hz), 7.55 (1H, dd, J=9.2 Hz,6.8 Hz), 6.05-5.87 (2H, br), 4.95-4.54 (1H, m), 4.38 (2H, m), 3.78-2.75(10H, m), 1. 16 (6H, t, J=7.0 Hz).

EXAMPLE 30(73)N-(4-butyloxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.32 (chloroform:methanol:acetic acid=40:1:1); NMR (DMSO-d₆): δ13.25-11.90Q(1H, br), 8.54-8.10 (1H, br), 7.89-7.65 (2H, m), 7.60-7.26(3H, m), 7.20-6.97 (2H, m), 6.28-5.49 (2H, br), 4.51 (2H, s), 4.40-4.09(1H, m), 4.06 (2H, t, J=6.2 Hz), 2.74-2.26 (2H, m), 1.87-1.58 (2H, m),1.58-1.26 (2H, m), 0.93 (3H, t, J=7.2 Hz).

EXAMPLE 30(74)N-(4-butyloxyphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

TLC:Rf 0.10 (chloroform:methanol:acetic acid=40:1:1); NMR (DMSO-d₆): δ13.52-11.75 (1H, br), 8.74-8.12 (1H, br), 8.00-7.67 (2H, m), 7.67-7.25(3H, m), 7.25-6.98 (2H, m), 6.15-5.48 (2H, br), 4.48-4.11 (1H, m), 4.26(2H, s), 4.02 (2H, t, J=6.4 Hz), 2.83-2.37 (2H, m), 1.84-1.55 (2H, m),1.55-1.24 (2H, m), 0.93 (3H, t, J=7.2 Hz).

EXAMPLE 31 (1)N-(4-phenylsulfinylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

By the same procedure as provided in example 8(1), using the compoundprepared in example 29(43), the compound of the present

TLC:Rf 0.12 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.00-7.88 and7.88-7.75 (4H, m), 7.70-7.56 and 7.53-7.43 (5H, m), 7.40-7.12 (3H, m),6.30-6.15 (1H, m), 5.80 (1H, d, J=17.8 Hz) 5.59 and 5.58 (total 1H, d,J=17.8 Hz), 4.60 (2H, s), 4.21-4.05 (1H, m), 2.78 (1H, dd, J=17.4 Hz,4.0 Hz), 2.28 and 2.27 (1H, dd, J=17.4 Hz, 4.6 Hz), 1.36 (9H, s).

EXAMPLE 32(1)N-(4-phenylsulfonylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

By the same procedure as provided in example 9(1), using the compoundprepared in example 29(43), the compound of the present

TLC:Rf 0.21 (hexane:ethyl acetate=2:1); NMR (CDCl₃): δ 8.10 (2H, d,J=8.0 Hz), 7.97 (2H, d, J=8.0 Hz), 7.98-7.90 (2H, m), 7.70-7.47 (3H, m),7.36 (1H, d, J=9.0 Hz), 7.36 (1H, d, J=7.0 Hz), 7.18 (1H, dd, J=9.0 Hz,7.0 Hz), 6.15 (1H, d, J=9.0 Hz), 5.82 and 5.62 (each 1H, d, J=17.8 Hz),4.60 (2H, s), 4.22-4.08 (1H, m), 2.78 (1H, dd, J=17.6 Hz, 4.0 Hz), 2.29(1H, dd, J=17.6 Hz, 4.6 Hz), 1.35 (9H, s).

EXAMPLE 33(1) AND EXAMPLE 33(2)

By the same procedure as provided in example 6(1), using the compoundprepared in example 31 (1) or example 32(1), the compounds of the

EXAMPLE 33(1)N-(4-phenylsulfinylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.10 (chloroform:methanol:acetic acid=50:1:1); NMR (DMSO-d₆): δ8.00 (2H, d, J=8.4 Hz), 7.96 (2H, d, J=8.4 Hz), 7.80-7.67 (2H, m),7.61-7.46 and 7.42-7.32 (6H, m), 6.00-5.62 (2H, br), 4.50 (2H, s),4.33-4.22 (1H, m), 2.57-2.37 (2H, m).

EXAMPLE 33(2)N-(4-phenylsulfonylphenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

TLC:Rf 0.14 (chloroform:methanol:acetic acid=50:1:1); NMR (CDCl₃): δ8.17 (2H, d, J=8:4 Hz), 8.06 (2H, d, J=8.4 Hz), 8.01-7.93 (2H, m),7.78-7.45 and 7.45-7.31 (6H, m), 6.03-5.68 (2H, br), 4.51 (2H, s),4.45-4.33 (1H, m), 2.65-2.52 (2H, m).

EXAMPLE 34(1)N-(4-aminophenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

By the same procedure as provided in reference example 9(1), using thecompound prepared in example 30(12), the compound of the present

TLC:Rf 0.29 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ8.50-7.80 (1H, br), 7.80-7.25 (5H, m), 6.61 (2H, d, J=8.8 Hz), 6.15-5.72(2H, m), 4.50 (2H, s), 3.97-3.81 (1H, m), 2.38-2.05 (2H, m).

EXAMPLE 35(1)N-(N,N-dibenzylamino)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.ethylester

To a solution of dibenzylamine (0.06 ml) in dimethylformamide (0.5 ml)was added 1,1′-carbonyldiimidazole (50 mg) at room,temperature under anatmosphere of argon. The mixture was stirred for 30 min. To the mixturewas added the compound prepared in reference example 11(2) (139 mg) indimethylformamide (0.5 ml) at 0° C. The mixture was stirred for roomtemperature overnight. The reaction mixture was quenched by addition of1 N successively, dried over anhydrous magnesium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane: ethyl acetate=1:1) to give the compound of thepresent invention (79 mg) having the following physical data. ethylacetate=1:1) to give the compound of the present invention (79 mg)

TLC:Rf 0.46 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.50-7.10 (13H,m), 5.59 (1H, d, J=8.2 Hz), 5.41 (1H, d, J=18.6 Hz), 5.23 (1H, d, J=18.6Hz), 4.84-4.66 (1H, m), 4.69-4.47 (2H, m), 4.29 (1H, d, J=16.6 Hz), 4.17(1H, d, J=16.6 Hz), 4.04 (2H, q, J=7.0 Hz), 3.02 (1H, dd, J=17.8 and 5.0Hz), 2.70 (1H, dd, J=17.8 and 4.8 Hz), 1.21 (3H, t, J=7.0 Hz).

EXAMPLE 36(1)N-(N,N-dibenzylamino)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

By the same procedure as provided in example 23(1), using the compoundprepared in example 35(1), the compound of the present invention

TLC:Rf 0.78 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ12.88-12.00 (1H, br), 7.65-7.06 (14H, m), 5.98-5.62 (2H, m), 4.82-4.62(1H, m), 4.59-4.13 (6H, m), 2.91 (1H, dd, J=17 and 7 Hz), 2.66 (1H, dd,J=17 and 7 Hz).

EXAMPLE 37(1)N-(N-benzyl-N-methylamino)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid.t-butylester

By the same procedure as provided in example 35(1), using the compoundprepared in reference example 9(1) instead of the compound prepared inreference example 11 (2) and N-benzyl-N-methylamine instead of NMR(CDCl₃): δ 7.40-7.16 (8H, m), 5.76 (1H, d, J=7.8 Hz), 5.53 (2H, s),

TLC:Rf 0.37 (hexane:ethyl acetate=1:1); NMR (CDCl₃): δ 7.40-7.16 (8H,m), 5.76 (1H, d, J=7.8 Hz), 5.53 (2H, s), 4.73 (1H, m), 4.53 (2H, s),4.30 (2H, m), 3.00 (3H, s), 2.98-2.67 (2H, m), 1.41 (9H, s).

EXAMPLE 38(1)N-(N-benzyl-N-methylamino)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid

By the same procedure as provided in example 6(1), using the compoundprepared in example 37(1), the compound of the present invention

TLC:Rf 0.28 (chloroform:methanol:acetic acid=10:1:1); NMR (DMSO-d₆): δ7.54-7.18 (9H, m), 5.81 (2H, brs), 4.60 (1H, m), 4.47 (2H, s), 4.32 (2H,m), 2.92-2.56 (5H, m).

EXAMPLE 39(1) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-aminophenylthio)tetrazol-2-yl)pentanoic acid

To the mixture solution of the compound prepared In example 5(157) Tothe mixture solution of the compound prepared In example 5(157) (770 mg)in methanol (11 ml) and water (3 ml) was added potassium carbonate (350mg). The reaction mixture was stirred for 7 h at room temperature. Thereaction mixture was added 1 N aqueous solution of hydrochloric aciduntil pH 4, extracted with ethyl acetate. The extract was columnchromatography on silica gel (chloroform:methanol:acetic acid=18:1:1) togive the compound of the present invention (235 mg) having the followingphysical data.

TLC:Rf 0.31 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ7.94 (1H, d, J=7.4 Hz), 7.46-7.24 (5H, m), 7.25 (2H, d, J=8.5 Hz), 6.59(2H, d, J=8.5 Hz), 5.90 (2H, brs), 5.72-5.20 (2H, br), 5.08 (2H, s),4.74-4.43 (1H, m), 2.90-2.50 (2H, m).

EXAMPLE 39(2) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-aminophenylthio)tetrazol-1-yl)pentanoic acid

By the same procedure as provided in example 39(1), using the compoundprepared in example 5(158) instead of the compound prepared in example5(157), compound of the present invention having the following physicaldata was obtained.

TLC:Rf 0.22 (chloroform:methanol:acetic acid=18:1:1); NMR (DMSO-d₆): δ13.50-11.50 (1H, br), 8.03 (1H, d, J=7.8 Hz), 7.46-7.22 (5H, m), 7.22(2H, d, J=8.6 Hz), 6.57 (2H, d, J=8.6 Hz), 5.94-5.30 (4H, br), 5.12 (2H,s), 4.73-4.50 (1H, m), 2.93-2.55 (2H, m).

EXAMPLE 40(1)N-(2-aminoethyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

By the same procedure as provided in reference example 9(1), using thecompound prepared in example 30(52), the compound of the presentinvention having the following physical data was obtained.

TLC:Rf 0.42 (chloroform:methanol:acetic acid=3:1:1); NMR (DMSO-d₀): δ13.00-12.40 (1H, br), 8.40-8.23 (1H, br), 8.23-8.00 (3H, br) 7.53 (1H,d, J=9.0 Hz), 7.52 (1H, d, J=7.0 Hz), 7.37 (1H, dd, J=9.0 Hz, 7.0 Hz),6.20-5.95 (2H, br), 4.53 (2H, s), 4.65-4.40 (1H, m), 3.61-3.00 (4H, m),3.00-2.65 (2H, m).

REFERENCE EXAMPLE 13N-(N-t-butyloxycarbonylamino)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

By the same procedure as provided in example 29(1), using the compoundprepared in reference example 9(2) instead of the compound prepared inreference example 9(1) and (N-t-butyloxycarbonylamino)sulfonyl chlorideinstead of 4-t-butylbenzenesulfonyl chloride, title compound having thefollowing physical data was obtained.

TLC:Rf 0.21 (hexane:ethyl acetate=2:1).

REFERENCE EXAMPLE 14N-(N-t-butyloxycarbonyl-N-benzylamino)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid.t-butylester

To a solution of the compound prepared In reference example 13 (548 mg)in tetrahydrofuran (7 ml) was added benzyl alcohol (0.14 ml),triphenylphosphine (361 mg) and diethylazodicarboxylate (0.55 ml) at 0°C. The reaction mixture was stirred for 2 h at room temperature. Thereaction chromatography on silica gel (hexane:ethyl acetate=5:1-2:1) togive the title compound having the following physical data.

EXAMPLE 41 (1)N-(N-benzylamino)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid

By the same procedure as provided in example 6(1), using the compoundprepared in reference example 14, the compound of the present inventionhaving the following physical data was obtained.

TLC:Rf 0.16 (chloroform:methanol:acetic acid=40:1:1). NMR (DMSO-d₆): δ13.00-11.60 (1H, br), 8.05-7.50 (1H, br), 7.70 (1H, t, J=6.1 Hz),7.62-7.43 (2H, m), 7.43-7.07 (6H, m), 6.19-5.74 (2H, m), 4.52 (2H, s),4.42-4.20 (1H, m), 4.10 (2H, d, J=6.1 Hz), 2.89-2.35 (2H, m).

EXAMPLE 42(1)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(methylaminocarbonylmethyl)tetrazol-2-yl)pentanoicacid

To a suspension of the compound prepared in example 5 (18) (190 mg) inmethanol (0.2 ml) was added 40% aqueous solution of methylamine (0.4ml). The reaction mixture was stirred for 5 h at room temperature. Thereaction mixture was quenched by addition of 1 N aqueous solution ofchromatography on silica gel (chloroform:methanol:acetic acid=20:1:1) togive the compound of the present invention (120 mg) having the followingchromatography on silica gel (chloroform:methanol:acetic acid=20:1:1) tochromatography on silica gel (chloroform:methanol:acetic acid=20:1:1) togive the compound of the present invention (120 mg) having the followingphysical data.

TLC:Rf 0.11 (chloroform:methanol:acetic acid=18:1:1). NMR (DMSO-d₆): δ8.15 (1H, d, J=5.0 Hz), 7.74 (1H, d, J=7.0 Hz), 7.53-7.13 (5H, m), 5.93(2H, s), 5.08 (2H, s), 4.64-4.33 (1H, m), 3.74 (2H, s), 2.70-2.48 (5H,m).

EXAMPLE 42(2)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(methylaminocarbonylmethyl)tetrazol-1-yl)pentanoicacid

By the same procedure as provided in example 42(1), using the compoundprepared in example 5(21) instead of the compound prepared in example5(18), the compound of the present invention having the followingphysical data was obtained.

TLC:Rf 0.08 (chloroform:methanol:acetic acid=18:1:1). NMR (DMSO-d₆): δ8.40 (1H, d, J=4.8 Hz), 7.87 (1H, d, J=7.6 Hz), 7.52-7.12 (5H, m),5.94-5.61 (2H, m), 5.08 (2H, s), 4.66-4.40 (1H, m), 3.80 (2H, s),2.85-2.49 (5H, m).

[FORMULATION EXAMPLE] Formulation Example 1

The following components were admixed in conventional manner and punchedout to obtain 100 tablets each containing 50 mg of active ingredient.

N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo- 5.0 g5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acidCarboxymethylcellulose calcium (disintegrating agent) 0.2 g Magnesiumstearate (lubricating agent) 0.1 g Microcrystalline cellulose 4.7 g

FORMULATION EXAMPLE 2

The following components were admixed in conventional manner. Thesolution was sterilized in conventional manner, placed 5 ml portion intoampoules and freeze-dried to obtain 100 ampoules each containing 20 mgof the active ingredient.

N-((N-(3-phenylpropionyl)-L-valyl)-L-alanyl)-3-amino-4-oxo- 2.0 g5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid mannitol 20g Distilled water 1000 ml

What is claimed is:
 1. A tetrazole derivative of formula (I), anon-toxic salt thereof, an acid addition salt thereof, or a hydratethereof:

wherein R is a hydrogen atom,

in which J is a bond, C1-6alkylene, C1-6oxyalkylene, C1-6aminoalkylene,C1-6thioalkylene, C2-6 alkenylene, carbocyclic ring or hetero ring,wherein the carbocyclic ring and hetero ring may be substituted by C1-4alkyl with the proviso that when J contains an oxygen atom, a nitrogenatom or a sulfur atom, the ozygen atom, the nitrogen atom or the sulfuratom is bonded to C═O or S(O)_(m) group in R; R¹ is 1) C1-8 alkyl, 2)C1-8 alkoxy, 3) C2-8 alkenyl, 4) C2-8 alkenyloxy, 5) C1-8 alkylamino, 6)di(C1-8 alkyl)amino, 7) C1-8 alkylthio, 8) Cyc¹ in which Cyc¹ is acarbocyclic ring or hetero ring, and Cyc¹ may be substituted by 1 to 5substituents selected from the group consisting of a hydrogen atom, C1-8alkyl, phenyl, phenyloxy, C1-8 alkyl substituted by phenyl, a halogenatom, nitro, trifluoromethyl, nitrile, keto, —OR², —NR²R³, —S(O)R²,—SO₂R², —COOR² or —COR², wherein R² is a hydrogen atom, C1-8 alkyl,phenyl or C1-4 alkyl substituted by phenyl, R³ is a hydrogen atom, C1-8alkyl, phenyl or C1-4 alkyl substituted by phenyl, C2-5 acyl, or R² andR³, taken together bonded to nitrogen atom, represent hetero ring, 9)Cyc¹—O— wherein Cyc¹ is the same as hereinbefore defined, 10) Cyc¹—S—wherein Cyc¹ is the same as herein before defined, 11) Cyc¹—CO— whereinCyc¹ is the same as hereinbefore defined, 12) C1-8 alkyl, C1-8 alkoxy,C1-8 alkylamino, di(C1-8 alkyl)amino or C1-8 alkylthio mono ordi-substituted by Cyc¹, Cyc¹—O—, Cyc¹—S—, or Cyc¹—CO— wherein Cyc¹ isthe same as hereinbefore defined, 13) trifluoromethyl, 14)Cyc¹—CO—NH—CH₂— wherein Cyc¹ is the same as hereinbefore defined, 15)amino, 16) benzyloxycarbonyl, 17) C2-5 acylamino, or 18) C1-8 alkoxysubstituted by C1-8 alkoxy; m is 0 or 1-2, with the proviso that (1)when m is 0, then —S(O)_(m)— is not directly bonded to a nitrogen atomor a sulfur atom, and (2) when m is 1, then —S(O)_(m)— is not directlybonded to a sulfur atom; AA¹ is 1) a bond or

 in which R⁴ is (1) a hydrogen atom, (2) C1-8 alkyl, (3) Cyc² in whichCyc² is a carbocyclic ring or hetero ring, and Cyc² may be substitutedby 1 to 5 substituents selected from the group consisting of a hydrogenatom, C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl, a halogenatom, nitro, trifluoromethyl, nitrile, tetrazole, —OR⁵, —NR⁵R⁶, —SR⁵,—COOR⁵ or —COR⁵, wherein R⁵ and R⁶ each, independently, is a hydrogenatom, C1-4 allyl, phenyl or C14 alkyl substituted by phenyl, or (4) C1-8alkyl substituted by a substituent selected from —OR⁷, —NR⁷R⁸, —SR⁷,—COOR⁷, —COR⁷, —CONH₂, —NR⁷—CO—NR⁷R⁸, guanidino or Cyc² in which R⁷ andR⁸ each, independently, is a hydrogen atom, C1-4 alkyl, phenyl or C1-4alkyl substituted by phenyl and Cyc² is the same as hereinbeforedefined; AA² is 1) a bond or

 in which R⁹ and R¹⁰ each, independently, is (1) a hydrogen atom, (2)C1-8 alkyl, (3) Cyc³ in which Cyc³ is a carbocyclic ring or hetero ring,and Cyc³ may be substituted by 1 to 5 substituents selected from thegroup consisting of a hydrogen atom, C1-8 alkyl, phenyl, C1-4 alkylsubstituted by phenyl, a halogen atom, nitro, trifluoromethyl, nitrile,tetrazole, —OR¹¹, —NR¹¹R¹², —SR¹¹, —COOR¹¹ or —COR¹¹, wherein R¹¹ andR¹² each, independently, is a hydrogen atom, C1-4 alkyl phenyl or C1-4alkyl substituted by phenyl, (4) C1-8 alkyl substituted by a substituentselected from —OR¹³, —NR¹³ R¹⁴, —SR¹³, —COOR¹³, —COR¹³, —CONH₂,—NR¹³—CO—NR¹³R¹⁴, guanidino or Cyc³ in which R¹³ is a hydrogen atom,C1-alkyl, phenyl or C1-4 alkyl substituted by phenyl, R¹⁴ is a hydrogenatom, C1-4 alkyl, phenyl, C1-4 alkyl substituted by phenyl,t-butyloxycarbonyl or benzyloxycarbonyl and Cyc³ is the same ashereinbefore defined or (5) R⁹ and R¹⁰, together, are a C1-6 alkylene orC2-6 alkenylene; AA¹ and AA², together, may have the formula:

in which R¹⁵ and R¹⁶ each, independently, is a hydrogen atom, C1-4alkyl, phenyl or C1-4 alkyl substituted by phenyl with the proviso thatC1-4 alkyl or phenyl may be substituted by C1-4 alkyl, C1-4 alkoxy, ahalogen atom, trifluoromethyl or phenyl; R¹⁷ is (1) a hydrogen atom, (2)C1-8 alkyl, (3) Cyc³ in which Cyc³ has the same meaning as hereinbeforedefined or (4) C1-8 alkyl substituted by a substituent selected from—OR¹³, —NR¹³R¹⁴, —SR¹³, —COOR¹³, —COR¹³, —CONH₂, —NR¹³—CO—NR¹⁴,guanidino or Cyc³ in which R¹³, R¹⁴ and Cyc³ are the same ashereinbefore defined; q is 2-12, with the proviso that a carbon atom in—(CH₂)_(q)— may be replaced by an oxygen atom, sulfur atom, —SO—, —SO₂—or —NR¹⁸— in which R¹⁸ is a hydrogen atom, C1-4 alkyl, phenyl or C1-4alkyl substituted by phenyl, or two hydrogen atoms at ortho positionsare replaced by a double bond, and Y is

in which R¹⁹ is a hydrogen atom, C1-8 alkyl, phenyl or C1-4 alkylsubstituted by phenyl; n is 1-4;

 or

Z is 1) C1-6 alkylene, 2) C2-6 alkenylene, 3) oxygen atom, 4) sulfuratom, 5) —CO—, 6) —SO—, 7) —SO₂—, 8) —NR²⁶— in which R²⁶ is a hydrogenatom, C1-4 alkyl, phenyl, C1-4 alkyl substituted by phenyl, or 9) acarbon atom in C1-6 alkylene replaced by an oxygen atom, sulfur atom,—CO—, —SO—, —SO₂— or —NR²⁶— in which R²⁶ is the same as hereinbeforedefined, with the proviso that Z is bonded directly to the carbon atomon a tetrazole ring; E is (1) a hydrogen atom, (2) a halogen atom, (3)C1-4 alkyl, (4) —COOR²⁷ in which R²⁷ is a hydrogen atom, C1-4 alkyl,phenyl, C1-4 substituted by phenyl, (5) —CONR²⁸R²⁹ in which R²⁸ and R²⁹each, independently, is a hydrogen atom, C1-4 alkyl, phenyl, C1-4substituted by phenyl or R²⁸ and R²⁹, taken together, bonded to nitrogenatom represent hetero ring or —NR²⁸R²⁹ in which R²⁸ and R²⁹ are the sameas hereinbefore defined, or

 in which

 is a carbocyclic ring or hetero ring, substituted by —(R²⁰)_(p) whereinR²⁰ is 1) a hydrogen atom, 2) C1-8 alkyl, 3) a halogen atom, 4) nitro,5) trifluoromethyl, 6) nitrile, 7) —OR²², 8) —NR²²R²³, 9) —SR²², 10)—COOR²², 11) —COR²² 12) —CONR²⁸R²⁹ in which R²⁸ and R²⁹ are the same ashereinbefore defined, 13) Cyc⁴ in which Cyc⁴ is a carbocyclic ring orhetero ring, and Cyc⁴ may be substituted by 1 to 5 substituents selectedfrom the group consisting of a hydrogen atom, C1-8 alkyl, phenyl, C1-4alkyl substituted by phenyl, a halogen atom, nitro, trifluoromethyl,nitrile, tetrazole, —OR²⁴, —NR²⁴R²⁵, —SR²⁴, —COOR²⁴ or —COR²⁴ in whichR²⁴ and R²⁵ each, independently, is a hydrogen atom, C1-4 alkyl, phenylor C1-4 alkyl substituted by phenyl, or 14) C1-8 alkyl substituted byCyc⁴ in which Cyc⁴ is the same as hereinbefore defined, R²² is ahydrogen atom, C1-4 alkyl, phenyl or C1-4 alkyl substituted by phenyl,R²³ is a hydrogen atom, C1-4 alkyl, phenyl, C1-4 alkyl substituted byphenyl, C2-5 acyl or trifluoromethylcarbonyl; p is 1-5; or —Z—E is ahalogen atom, trifluoromethyl, C1-4 alkyl di-substituted by phenyl ortri(C1-4 alkyl) silyl with the proviso that (1) when Z is C1-6 alkyleneor C2-6 alkenylene, E is now a hydrogen atom or C1-4 alkyl, (2) when Zis —SO—, E is not a hydrogen atom, or (3) at least one of J, Cyc¹, Cyc²,Cyc³, Cyc⁴, and

represents a hetero ring, (4) when J, Cyc¹, Cyc², Cyc³, Cyc⁴ and

 represent a carbocyclic ring at the same time, then R² and R³, takentogether bonded to nitrogen atom represents hetero ring, (5) when J,Cyc¹, Cyc², Cyc³, Cyc⁴ and

 represent a carbocyclic ring at the same time, then R²⁸ and R²⁹, takentogether bonded to nitrogen atom, represent hetero ring, (6) when J,Cyc¹, Cyc², Cyc³, Cyc⁴ and

 represent a carbocyclic ring at the same time, then R⁹ and R¹⁰,together are a C1-6 alkylene or C2-6 alkenylene, or (7) when J, Cyc¹,Cyc⁴ and

 represent a carbocyclic ring at the same time, then AA¹ and AA²,together, may have the formula;


2. The compound according to claim 1, wherein the E group in Y is ahydrogen atom, halogen atom, C1-4 alkyl, —CO OR²⁷, CONR²⁸R²⁹ or —NR²⁸R²⁹in which R²⁷, R²⁸ and R²⁹ are defined as in claim
 1. 3. The compoundaccording to claim 1, wherein the E group in Y is

in which R²⁰ and p are defined as in claim 1, and

is a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring.
 4. Thecompound according to claim 1, wherein the E group in Y is

in which R²⁰ and p are defined as in claim 1, and

is a 5-18 membered mono-cyclic, bi-cyclic or tri-cyclic hetero ringcontaining 1-3 nitrogen atoms, one oxygen atom or one sulfur atom. 5.The compound according to claim 1, wherein the —Z—E group in Y is ahalogen atom, trifluromethyl, diphenylmethyl or tri(C1-alkyl)silyl. 6.The compound according to claim 1, wherein AA¹ is α-amino acid residueand AA² is α-amino acid residue.
 7. The compound according to claim 1,wherein AA¹ is a bond and AA² is α-amino acid residue.
 8. The compoundaccording to claim 1, wherein AA¹ is a bond and AA² is a bond.
 9. Thecompound as in any one of claims 1 to 3, wherein AA¹ and AA² takentogether, represent

in which R¹⁵, R¹⁶, R¹⁷ and q are defined as in claim
 1. 10. A compoundaccording to claim 1, which is (1)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrrol-2-yl methyl)tetrazol-2-yl)pentanoic acid, (2)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrrol-2-ylmethyl)tetrazol-1-yl)pentanoic acid, (3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-2-ylmethyl)tetrazol-2-yl)pentanoicacid, (4)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-2-ylmethyl)tetrazol-1-yl)pentanoicacid, (5)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-3-ylmethyl)tetrazol-2-yl)pentanoicacid, (6)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-3-ylmethyl)tetrazol-1-yl)pentanoicacid, (7)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-4-yl)tetrazol-2-yl)pentanoic acid, (8)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(pyridin-4-yl)tetrazol-1-yl)pentanoic acid, (9)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1l-methylpyrimidin-2,4-dion-3-ylmethyl)tetrazol-2-yl)pentanoicacid, (10)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(1-methylpyrimidin-2,4-dion-3-ylmethyl)tetrazol-1-yl)pentanoicacid, (11) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imidazol-1-ylmethyl)tetrazol-2-yl)pentanoic acid, (12) N-benzyloxycarbonyl-3-amino-4-o-(5-(imidazol-1-ylmethyl) tetrazol-1-yl)pentanoic acid, (13)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiophen-2-yl)tetrazol-2-yl)pentanoic acid, (14)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazo-2-yl)tetrazol-1-yl)pentanoic acid, (15)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazo-3-yl)tetrazol-2-yl)pentanoic acid, (16)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazo-3-yl)tetrazol-1-yl)pentanoic acid, (17)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-imidazol-1-ylpropyl)tetrazol-2-yl)pentanoic acid, (18)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-imidazol-1-ylpropyl)tetrazol-1-yl)pentanoic acid, (19)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,2,6,6-tetramethylpiperidin-2-ylmethyl)tetrazol-2-yl)pentanoicacid, (20)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2,2,6,6-tetramethylpiperidin-1-ylmethyl)tetrazol-1-yl)pentanoicacid, (21)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzoimizazol-2-ylmethyl)tetrazol-2-yl)pentanoic acid, (22)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzoimizazol-2-ylmethyl)tetrazol-1-yl)pentanoic acid, (23)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzothiazol-2-ylmethyl)tetrazol-2-yl)pentanoic acid, (24)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(benzothiazol-2-ylmethyl)tetrazol-1- yl)pentanoic acid, (25)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-2-ylthio)tetrazol-2-yl)pentanoicacid, (26)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(thiazol-2-ylthio)tetrazol-1-yl)pentanoicacid, (27)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(5-imidazol-1-ylpentyl)tetrazol-2-yl)pentanoic acid, (28)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(5-imidazol-1-ylpentyl)tetrazol-1-yl)pentanoic acid, (29)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-fluorophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid, (30)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-fluorophenyl)thiazol-2-ylmethyl)tetrazol-1-yl)pentanoicacid, (31)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-chlorophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid, (32)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(4-chlorophenyl)thiazol-2-ylmethyl)tetrazol-1-yl)pentanoicacid, (33)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(3-nitrophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid, (34)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(3-nitrophenyl)thiazol-2-ylmethyl)tetrazol-2-yl)pentanoicacid, (35) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imizazol-4-ylmethyl)tetrazol-2-yl)pentanoic acid, (36)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imizazol-4-ylmethyl)tetrazol-1-yl)pentanoic acid, (37)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)ethenyl)tetrazol-2-yl)pentanoic acid, (38)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)ethenyl)tetrazol-1-yl)pentanoic acid, (39)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)ethyl)tetrazol-2-yl)pentanoic acid, (40)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)ethyl)tetrazol-1-yl)pentanoic acid, (41)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imidazol-2-ylmethyl)tetrazol-2-yl)pentanoic acid, or (42)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(imidazol-2-ylmethyl)tetrazol-1-yl)pentanoic acid, an ester thereof, a non-toxic saltthereof, an acid addition salt thereof or a hydrate thereof.
 11. Acompound according to claim 1, which is (1)3-(N-(2S-(2-phenyl-4R-methyl-4,5-dihydrothiazol-4-ylcarbonylamino)propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, (2)3-(N-(2S-(2-phenyl-4,5-dihydrothiazol-4-ylcarbonylamino)propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid,(3)(N-(1-benzyloxycarbonylpiperidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, (4)N-(1-acetylpiperidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, (5)N-(1-benzyloxycarbonylpyrrolidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, or (6)N-(1-acetylpyrrolidin-2S-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, or and ester thereof, a non-toxic salt thereof, an acid additionsalt thereof or a hydrate thereof.
 12. A compound according to claim 1,which is (1) N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(3-(imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoic acid, (2)N-benzyloxycarbonyl-3-amino-4oxo-5-(5-(3-(imidazol-2-yl)phenylmethyl)tetrazol-1-yl)pentanoic acid, (3)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoic acid, (4)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(4-(imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoic acid, (5)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoic acid, (6)N-benzyloxycarbonyl-3-amino-4-oxo-5-(5-(2-(imidazol-2-yl)phenylmethyl)tetrazol-2-yl)pentanoic acid, (7)N-(2-(thiazo-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid, (8)N-(2-(thiazo-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyltetrazol-1-yl)pentanoic acid, (9)N-(2-(pyridin-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (10)N-(2-(pyridin-2-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid, (11)N-2-(4-methylthiazol-5-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid, (12)N-(2-(4-methyl-1-thiazo1-5-yl)ethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid, (13)N-(2-phenylethylthio)carbonyl-3-oxo-4-oxo-5-(5-(4-(pyrrolidin-1-ylmethyl)phenylthio)tetrazol-2-yl)pentanoicacid, (14)N-(2-phenylethylthio)carbonyl-3-amino-4-oxo-5-(5-(4-(pyrrolidin-1-ylmethyl)phenylthio)tetrazol-2-yl)pentanoicacid, (15)N-(2-(4-methylthiazol-5-yl)ethylthio)carbonyl-3-amino4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid, (16)N-(2-(4methylthiazol-5-yl)ethylthio)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoicacid, (17)N-3-(pyrimidin-2-yl)propyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-2-yl)pentanoicacid, (18)N-3-(pyrimidin-2-yl)propyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylthio)tetrazol-1-yl)pentanoic acid, (19)N-(thiazo-4-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (20)N-perhydrobenzo-1,4-diazepin-2,5-dion-3-ylcarbonyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (21)N-(2-hexahydro-2-oxo-azepin-1-yl)propionyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, (22)N-(2S-(tetrahydro-5-oxo-1,4-benzooxsazepin-4-yl)propionyl)-3-amino4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, (23)N-(2S-(2,3-indol-3,4-tetrahydro-2-oxoazepin-1-yl)propionyl)-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, (24)N-(pyridin-4-ylmethyloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid, (25)N-(tetrahydrofuran-3-yloxy)carbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid, (26)N-(quinolin-8-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (27)N-(thiazo-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid, (28)N-(5-(pyridin-2-yl)thiazo-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (29)N-1-(3chloro-5-trifluoromethylpyridin-2-yl)pyrrol-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (30)N-(2-acetylamino-4-methylthiazol-5-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid (31)N-(benzofurazan-4-yl)sulfonyl-3-amino-4-oxo-5-(5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (32)N-(3,5dimethylisooxazol-4-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid, (33)N-(1,1-dioxotetrahydrothiophen-3-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (34)N-(5-phenylcarbonylaminomethylthiophen-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (35)N-(2,1,3-benzothiadiazol-4-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoic acid, (36)N-(6-chloroimizazo[2,1-B]thiazol-5-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (37)N-(5-(2-methylthiopyrimidin4yl)thiazo-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (38)N-5-(isooxazol-3-yl)thiazo-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (39)N-(5-(4-chlorophenylcarbonylaminomethyl)thiazo-2-yl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (40)N-4-(pyrrolidin-1-yl)phenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid, or (41)N-4-(morpholin-4-yl)phenyl)sulfonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid, or an ester thereof, an non-toxic saltthereof, an acid addition salt thereof or hydrate thereof.
 13. Acompound according to claim 1, which is (1)3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, (2) 3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-2-yl)pentanoicacid, (3) 3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoic acid, (4)3-(N-(2-(hexahydro-2-oxo-3S-(thiazol-4-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoicacid, (5)3-(N-(2-(hexahydro-2-oxo-3S-(thiazol-4-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoic acid, (6)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (7)3-(N-(2-(hexahydro-2-oxo-3S-(quinolin-2-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (8)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-2-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (9)3-(N-(2-(hexahydro-2-oxo-3S-(morpholin-1-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (10)3-(N-(2-(hexahydro-2-oxo-3S-(pyridin-4-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (11) 3-(N-(2-(hexahydro-2-oxo-3S-(4-methoxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (12) 3-(N-(2-(hexahydro-2-oxo-3S-(3-methoxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (13) 3-(N-(2-(hexahydro-2-oxo-3S-(4-(morpholin-1-ylcarbonyl)phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (14)3-(N-(2-(hexahydro-2-oxo-3S-(quinolin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (15)³-(N-(2-(hexahydro-2-oxo-3S-(pyridin-3-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid, (16)3-(N-(2-(hexahydro-2-oxo-3S-(4-dimethylaminophenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (17) 3-(N-(2-(hexahydro-2-oxo-3S-(3-carboxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (18) 3-(N-(2-(hexahydro-2-oxo-3S-(4-carboxyphenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, (19)3-(N-(2-(hexahydro-2-oxo-3S-(imidazol-5-ylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-phenylmethyltetrazol-1-yl)pentanoicacid, or (20)N-(2-(4-fluorophenyl)-4-oxo-5-benzyloxocarbonylaminopyrimidin-3-yl)methylcarbonyl-3-amino-4-oxo-5-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl)pentanoic acid.
 14. A compound according to claim 1, which is3-(N-(2-(hexahydro-2-oxo-3S-(phenylcarbonylamino)azepin-1-yl))propionyl)amino-4-oxo-5-(5-trifluoromethyltetrazol-2-yl) pentanoic acid, or andester thereof, a non-toxic salt thereof, an acid addition salt thereofor a hydrate thereof.
 15. A pharmaceutical composition which comprises,as an active ingredient, an effective amount of a compound of formula(1) according to claim 1, a non-toxic salt thereof, an acid additionsalt thereof or a hydrate thereof, and a pharmaceutically acceptablecarrier or coating.
 16. A method for the prevention and/or the treatmentin a patient of diseases induced by interleukin-1β converting enzyme,which comprises the administration to a patient of an effective amountof a compound of formula (I) according to claim 1, a non-toxic saltthereof, a non-toxic acid addition salt thereof or hydrate thereof. 17.A method for the prevention and/or the treatment in a patient of insulindependent diabetes (type I), multiple sclerosis, acute or delayed typehypersensitivity, infectious diseases, infectious complications, septicshock, arthritis, colitis, glomelular nephritis, hepatitis, hepaticcirrhosis, pancreatitis, reperfusion injury, cholangeitis, encephalitis,endocarditis, myocarditis, vasculitis, Alzheimer's disease, Parkinson'sdisease, dementia, cerebral vascular disturbance, neuro-degenerativediseases, bone or cartilage-resorption disease, AIDS, ARC (AIDS) relatedcomplex), adult T cell leukemia, hairy cell (pilocytic) leukemia,myelosis, respiratory dysfunction, arthropathy, uveitis, neoplasm,diffuse collagen diseases, ulcerative colitis, Sjogren's syndrome,primary biliary cirrhosis, idiopathic thrombocytopnic purpura,autoimmonohaemolytic anemia, severe myasthenia, osteodisplasia syndrome,periodic thrombocytopenia, aplastic anemia, idiopathic thrombocytopenia,diseases accompanied with thrombocytopenia, adult dyspnea syndrome,hyperplasia of the prostatic gland, myaoma of the uterus, asthmabronchial, arteriosclerosis, congenital teratoma, nephritis, senilecataract, chronic fatigue syndrome, myodystrophy or peripheral nervousdisturbance, which comprises the administration to a patient of aneffective amount of a compound of formula (I) according to claim 1, anon-toxic salt thereof, a non-toxic acid addition salt thereof or ahydrate thereof.